g(m1)-ganglioside and Guillain-Barre-Syndrome

Acute motor axonal neuropathy (AMAN) is a pure motor axonal subtype of Guillain-Barré syndrome (GBS) that was identified in the late 1990s. In Asia and Central and South America, it is the major subtype of GBS, seen in 30-65% of patients. AMAN progresses more rapidly and has an earlier peak than demyelinating GBS; tendon reflexes are relatively preserved or even exaggerated, and autonomic dysfunction is rare. One of the main causes is molecular mimicry of human gangliosides by Campylobacter jejuni lipo-oligosaccharides. In addition to axonal degeneration, electrophysiology shows rapidly reversible nerve conduction blockade or slowing, presumably due to pathological changes at the nodes or paranodes. Autoantibodies that bind to GM1 or GD1a gangliosides at the nodes of Ranvier activate complement and disrupt sodium-channel clusters and axoglial junctions, which leads to nerve conduction failure and muscle weakness. Improved understanding of the disease mechanism and pathophysiology might lead to new treatment options and improve the outlook for patients with AMAN.

Topics: Animals; Autoantibodies; Autoantigens; Axons; Campylobacter Infections; Campylobacter jejuni; Complement Activation; Diagnosis, Differential; Disease Models, Animal; Electrodiagnosis; G(M1) Ganglioside; Global Health; Guillain-Barre Syndrome; Humans; Immunoglobulins, Intravenous; Molecular Mimicry; Motor Neurons; Neural Conduction; Plasma Exchange; Randomized Controlled Trials as Topic; Ranvier's Nodes; Reflex, Abnormal; Sodium Channels

Guillain-Barré syndrome (GBS) is a rare autoimmune disorder, the incidence of which is estimated to be 0.6-4/100,000 person/year worldwide. Often, GBS occurs a few days or weeks after the patient has had symptoms of a respiratory or gastrointestinal microbial infection. The disorder is sub-acute developing over the course of hours or days up to 3 to 4 weeks. About a third of all cases of Guillain-Barré syndrome are preceded by Campylobacter jejuni infection. C. jejuni strains isolated from GBS patients have a lipooligosaccharide (LOS) with a GM1-like structure. Molecular mimicry between LOS and the peripheral nerves as a cause of GBS was demonstrated in animal models of human GBS. Following the "swine flu" virus vaccine program in the USA in 1976, an increase in incidence of GBS was observed and the calculated relative risk was 6.2. Later studies have found that influenza vaccines contained structures that can induce anti-GM1 (ganglioside) antibodies after inoculation into mice. More recent information has suggested that the occurrence of GBS after currently used influenza and other vaccines is rare. GBS involves genetic and environmental factors, may be triggered by infections or vaccinations, and predisposition can be predicted by analyzing some of these factors.

Topics: Adverse Drug Reaction Reporting Systems; Animals; Autoantibodies; Centers for Disease Control and Prevention, U.S.; Disease Models, Animal; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Infections; Influenza Vaccines; Lipopolysaccharides; Mice; Molecular Mimicry; Peripheral Nerves; United States; United States Food and Drug Administration; Vaccination

Our mechanistic understanding of the Guillain-Barre' syndromes (GBS) was greatly enhanced by the human pathological studies of Jack Griffin and colleagues conducted in the mid-1990s. Subsequently, many of the pathological findings in human GBS were confirmed and extended in animal models. This brief account of GBS pathogenesis focuses on the studies that provided the mechanistic evidence for the role of anti-ganglioside antibodies and complement in injuring the motor axon in Campylobacter-associated GBS, thereby supporting the earlier seminal pathological observations.

Topics: Animals; Autoantibodies; Autoantigens; Axons; Disease Models, Animal; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Motor Neurons

Guillain-Barré syndrome (GBS), characterized by acute progressive limb weakness and areflexia, is the prototype of postinfectious autoimmune diseases. Campylobacter jejuni is the most frequently identified agent of infection in GBS patients, often preceding acute motor axonal neuropathy (AMAN), a variant of GBS. Anti-GM1, anti-GM1b, anti-GD1a, and anti-GalNAc-GD1a IgG antibodies are associated with AMAN. Carbohydrate mimicry [Galbeta1-3GalNAcbeta1-4(NeuAcalpha2-3)Galbeta1-] was seen between the lipo-oligosaccharide of C. jejuni isolated from an AMAN patient and human GM1 ganglioside. Sensitization with the lipo-oligosaccharide of C. jejuni induces AMAN in rabbits as does sensitization with GM1 ganglioside. Paralyzed rabbits have pathological changes in their peripheral nerves identical to changes seen in human GBS. C. jejuni infection may induce anti-ganglioside antibodies by molecular mimicry, eliciting AMAN. This is the first verification of the causative mechanism of molecular mimicry in an autoimmune disease. To express ganglioside mimics, C. jejuni requires specific gene combinations that function in sialic acid biosynthesis or transfer. The knockout mutants of these landmark genes of GBS show reduced reactivity with GBS patients' sera, and fail to induce an anti-ganglioside antibody response in mice. These genes are crucial for the induction of neuropathogenic cross-reactive antibodies. An approach for evaluating intravenous immune globulin, a treatment for GBS, based on our animal model of AMAN is also discussed in this review, and recent advances made in this field are described.

Topics: Animals; Antigens, Bacterial; Autoantibodies; Campylobacter Infections; Disease Models, Animal; G(M1) Ganglioside; Gangliosides; Guillain-Barre Syndrome; Humans; Molecular Mimicry; Oligosaccharides

Progress has been made in our understanding of Guillain-Barré syndrome, especially in identifying the Campylobacter jejuni genes responsible for the development of clinical features.. C. jejuni is grouped into several classes based on the organization of lipo-oligosaccharide biosynthesis genes. A specific class carrying a sialyltransferase gene (cst-II) is associated with the development of Guillain-Barré syndrome, which is essential for the biosynthesis of ganglioside-like lipo-oligosaccharides. The class of C. jejuni expressed both GM1-like and GD1a-like lipo-oligosaccharides, which could induce the production of autoantibodies to GM1, to GD1a or to the GM1/GD1a complex, possibly increasing the risk of development. C. jejuni sialyltransferase (Cst-II) consists of 291 amino acids, and the 51st amino acid determines its enzymatic activity. Strains with cst-II (Thr51) expressed GM1-like or GD1a-like lipo-oligosaccharide whereas strains with cst-II (Asn51) expressed GT1a-like or GD1c-like lipo-oligosaccharide. Patients infected with the cst-II (Thr51) strains had anti-GM1 or anti-GD1a IgG antibodies, and showed limb weakness. Patients infected with the cst-II (Asn51) strains had anti-GQ1b IgG antibodies, and showed ophthalmoplegia and ataxia.. The cst-II gene is responsible for the development of Guillain-Barré and Fisher syndromes, and the polymorphism (Thr/Asn51) determines which syndrome develops after C. jejuni enteritis.

Topics: Animals; Antibodies, Bacterial; Autoantibodies; Campylobacter Infections; Campylobacter jejuni; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Miller Fisher Syndrome; Sialyltransferases

Topics: Campylobacter jejuni; Distal Myopathies; Drug Therapy, Combination; G(M1) Ganglioside; Guillain-Barre Syndrome; Haplotypes; HLA-DR3 Antigen; Humans; Immunoglobulins, Intravenous; Lipopolysaccharides; Methylprednisolone; Mutation; Myositis, Inclusion Body; Neuromuscular Diseases; Randomized Controlled Trials as Topic

Topics: Autoantibodies; Enzyme-Linked Immunosorbent Assay; G(M1) Ganglioside; Gangliosides; Guillain-Barre Syndrome; Humans; Miller Fisher Syndrome; Ophthalmoplegia; Reference Values; Specimen Handling

Campylobacter jejuni is the most frequent agent of antecedent infection in an axonal variant of Guillain-Barré syndrome, acute motor axonal neuropathy, and anti-GM1 or anti-GD1a IgG antibody is also associated with acute motor axonal neuropathy. Molecular mimicry has been found between human GM1 ganglioside and the lipo-oligosaccharide of C. jejuni isolated from an acute motor axonal neuropathy patient. Progress has been made in Guillain-Barré syndrome research, especially on acute motor axonal neuropathy subsequent to C. jejuni enteritis.. Sensitization of rabbits with C. jejuni lipo-oligosaccharide, as well as GM1, induced the production of anti-GM1 IgG antibody, and the subsequent development of acute flaccid paralysis. Pathological changes in rabbit peripheral nerves were identical to those seen in human acute motor axonal neuropathy. These findings provide conclusive evidence that molecular mimicry is a cause of human autoimmune disease. Ganglioside-like lipo-oligosaccharide is synthesized by sialyltransferase Cst-II, N-acetylgalactosaminyl-transferase CgtA, and galactosyltransferase CgtB. There is a strong association between the simultaneous presence of these genes and Guillain-Barré syndrome-associated C. jejuni strains. Knockout mutants of C. jejuni genes involved in lipo-oligosaccharide sialylation had reduced reactivity with anti-GM1 sera from Guillain-Barré syndrome patients, and did not induce an anti-GD1a IgG antibody response in mice. Lipo-oligosaccharide biosynthesis genes appear to be essential for the induction of anti-GM1 or anti-GD1a IgG antibody and the subsequent development of acute motor axonal neuropathy.. The concept that carbohydrate mimicry causes autoimmune disease provides a clue to the resolution of the pathogenesis of other immune-mediated diseases.

Topics: Animals; Autoantibodies; Campylobacter Infections; Campylobacter jejuni; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans

Topics: Animals; Autoantibodies; Autoimmunity; Disease Models, Animal; Epitopes; G(M1) Ganglioside; Gangliosides; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Nerve Fibers, Myelinated; Neural Conduction; Ranvier's Nodes

Topics: Alzheimer Disease; Biomarkers; G(M1) Ganglioside; Guillain-Barre Syndrome; Hematologic Tests; Humans; Motor Neuron Disease; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Specimen Handling

Topics: Acute Disease; Aged; Antibodies, Antinuclear; Antibody Specificity; Autoantibodies; Autoimmune Diseases; Evoked Potentials; Female; France; G(M1) Ganglioside; Gastroenteritis; Guillain-Barre Syndrome; Humans; Immunoglobulin M; Neurologic Examination

Topics: Antibody Specificity; Autoantibodies; Autoantigens; Autoimmune Diseases; Brain; Carbohydrate Sequence; CD57 Antigens; Chronic Disease; G(M1) Ganglioside; Gangliosides; Globosides; Glycolipids; Guillain-Barre Syndrome; Humans; Immunoglobulin M; Molecular Sequence Data; Motor Neuron Disease; Myelin Sheath; Paraproteinemias; Peripheral Nervous System; Polyradiculoneuropathy; Sulfoglycosphingolipids

Some patients develop Guillain-Barré syndrome (GBS) after the administration of bovine gangliosides. Patients with GBS subsequent to Campylobacter jejuni enteritis frequently have IgG antibody to GM1 ganglioside. Miller Fisher syndrome (MFS), a variant of GBS, is associated with IgG antibody to GQ1b ganglioside. Molecular mimicry between GM1 and lipopolysaccharide of C. jejuni isolated from patients with GBS, and between GQ1b and C. jejuni lipopolysaccharides from patients with MFS have been demonstrated. The molecular mimicry between infectious agents and gangliosides may function in the production of anti-ganglioside antibodies. This sugar mimicry is one possible cause of the Guillain-Barré and Miller Fisher syndromes; however, unidentified host factors may contribute to the development of these syndromes.

Topics: Animals; Antigens, Bacterial; Autoantigens; Autoimmune Diseases; Campylobacter Infections; Campylobacter jejuni; Cattle; Epitopes, B-Lymphocyte; G(M1) Ganglioside; Gangliosides; Guillain-Barre Syndrome; Humans; Lipopolysaccharides; Miller Fisher Syndrome; Molecular Mimicry

Topics: Autoantibodies; Biomarkers; Campylobacter jejuni; Cytomegalovirus; G(M1) Ganglioside; Gangliosides; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Immunoglobulin M; Immunoglobulins, Intravenous; Plasma Exchange; Prognosis

Some patients developed Guillain-Barré syndrome (GBS) after the administration of bovine gangliosides. Patients with GBS subsequent to Campylobacter jejuni enteritis frequently have IgG antibody to GM1 ganglioside. Miller Fisher syndrome (MFS), a variant of GBS, is associated with IgG antibody to GQ1b ganglioside. We showed the existence of molecular mimicry between GM1 and lipopolysaccharide of C. jejuni isolated from patients with GBS, and that between GQ1b and C. jejuni lipopolysaccharides from patients with MFS. The molecular mimicry between infectious agents and gangliosides may function in the production of anti-ganglioside antibodies. This sugar mimicry is one possible cause for GBS and MFS, and unidentified host factor may contribute to the development of these syndromes.

Topics: Autoantibodies; Campylobacter Infections; Campylobacter jejuni; Enteritis; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Lipopolysaccharides; Miller Fisher Syndrome; Molecular Mimicry

Recent neurophysiological and pathological studies have led to a reclassification of the diseases that underlie Guillain-Barré syndrome (GBS) into acute inflammatory demyelinating polyradiculoneuropathy (AIDP), acute motor and sensory axonal neuropathy (AMSAN) and acute motor axonal neuropathy (AMAN). The Fisher syndrome of ophthalmoplegia, ataxia and areflexia is the most striking of several related conditions. Significant antecedent events include Campylobacter jejuni (4-66%), cytomegalovirus (5-15%), Epstein-Barr virus (2-10%), and Mycoplasma pneumoniae (1-5%) infections. These infections are not uniquely associated with any clinical subtype but severe axonal degeneration is more common following C. jejuni and severe sensory impairment following cytomegalovirus. Strong evidence supports an important role for antibodies to gangliosides in pathogenesis. In particular antibodies to ganglioside GM1 are present in 14-50% of patients with GBS, and are more common in cases with severe axonal degeneration associated with any subtype. Antibodies to ganglioside GQ1b are very closely associated with Fisher syndrome, its formes frustes and related syndromes. Ganglioside-like epitopes exist in the bacterial wall of C. jejuni. Infection by this and other organisms triggers an antibody response in patients with GBS but not in those with uncomplicated enteritis. The development of GBS is likely to be a consequence of special properties of the infecting organism, since some strains such as Penner 0:19 and 0:41 are particularly associated with GBS but not with enteritis. It is also likely to be a consequence of the immunogenetic background of the patient since few patients develop GBS after infection even with one of these strains. Attempts to match the subtypes of GBS to the fine specificity of anti-ganglioside antibodies and to functional effects in experimental models continue but have not yet fully explained the pathogenesis. T cells are also involved in the pathogenesis of most or perhaps all forms of GBS. T cell responses to any of three myelin proteins, P2, PO and PMP22, are sufficient to induce experimental autoimmune neuritis. Activated T cells are present in the circulation in the acute stage, up-regulate matrix metalloproteinases, cross the blood-nerve barrier and encounter their cognate antigens. Identification of the specificity of these T cell responses is still at a preliminary stage. The invasion of intact myelin sheaths by activated macrophages is diffi

Topics: Animals; Campylobacter jejuni; Cytomegalovirus Infections; Demyelinating Diseases; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Mice; Miller Fisher Syndrome; Neuritis, Autoimmune, Experimental; Refsum Disease

To compare the effects of intravenous immunoglobulin (IVIg) therapy and plasmapheresis for the IgG anti-GM1-positive subtype of Guillain-Barré syndrome (GBS), clinical and electrophysiological recoveries were analyzed in 24 patients treated with IVIg (n = 10) or plasmapheresis (n = 14). At entry, there were no significant differences between the two patient groups in age, sex, clinical severity (Hughes grade), sum scores of distally evoked amplitudes of compound muscle action potentials (CMAPs), and frequency of Campylobacter jejuni infection. The patients treated with IVIg had significantly lower Hughes grade scores 1, 3, and 6 months after onset (P = 0.03), and a higher probability to regain independent locomotion at 6 months [P(logrank) = 0.044]. In the IVIg group, markedly rapid recovery (improvement by two or more Hughes grade scores within 4 weeks) was more frequent (6 of 10 vs. 3 of 14, P = 0. 03), and delayed recovery (unable to walk independently at 6 months) was less frequent (0 of 10 vs. 4 of 14, P = 0.06). CMAP sum score at 6 months tended to be greater for the IVIg group (P = 0.07). For the IgG anti-GM1-positive subgroup of GBS patients, IVIg therapy may be a more efficacious treatment than plasmapheresis.

Topics: Action Potentials; Adult; Demography; Electrodiagnosis; Female; Follow-Up Studies; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Immunoglobulins, Intravenous; Male; Plasmapheresis; Recovery of Function; Remission Induction; Severity of Illness Index; Treatment Outcome

To test the hypothesis that different preceding infections influence the neurophysiologic classification and clinical features of Guillain-Barré syndrome (GBS).. We tested pretreatment sera, 7 +/- 3 (mean +/- SD) days from onset, from 229 patients with GBS in a multicenter trial of plasma exchange and immunoglobulin, for serological markers of infection, adhesion molecules, and cytokine receptors, and compared these with neurophysiologic and clinical features.. Recent infection by Campylobacter jejuni was found in 53 patients (23%), cytomegalovirus in 19 (8%), and Epstein-Barr virus in four (2%). Patients with C. jejuni infection were more likely than others to have neurophysiologic criteria of axonal neuropathy or inexcitable nerves, antiganglioside GM(1) antibodies, pure motor GBS, lower CSF protein, and worse outcome. Patients with cytomegalovirus infection were younger and more likely than others to have raised serum concentrations of molecules important in T lymphocyte activation and migration, soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble leukocyte selectin, and soluble interleukin-2 receptor (sIL-2R). Concentrations of sICAM-1 and soluble tumor necrosis factor receptor were higher in patients with inexcitable nerves than those with demyelinating neurophysiology. Logistic regression analysis showed death or inability to walk unaided at 48 weeks were associated with diarrhea, inexcitable nerves, severe arm weakness, age over 50, raised sIL-2R concentration and absence of immunoglobulin (Ig) M antiganglioside GM(1) antibodies.. Subtypes of GBS defined by preceding infections were only approximately associated with different patterns of clinical, neurophysiologic, and immunologic features. A single infectious agent caused more than one type of pathology in GBS, implying interaction with additional host factors. Most patients had no identified infection.

Topics: Antibodies; Bacterial Infections; Cell Adhesion Molecules; Enzyme-Linked Immunosorbent Assay; G(M1) Ganglioside; Guillain-Barre Syndrome; Herpesvirus 4, Human; Humans; Prognosis; Receptors, Cytokine; Regression Analysis

N-Glycolylneuraminic acid-containing GM1 [GM1(Gc)] is a molecule for serum antibodies in patients with Guillain-Barré syndrome (GBS). To clarify the pathogenesis of GBS after treatment with bovine brain ganglioside, we investigated the presence of anti-GM1(Gc) antibody in patients who developed GBS after ganglioside injection. Serum samples were taken from nine Italian patients with GBS after ganglioside therapy as well as from untreated Italian (n=30) and Japanese (n=131) GBS patients. Bovine brain gangliosides fractionated in a column were used as antigens, and binding of serum IgG or IgM was examined. An absorption study of IgG anti-GM1(Gc) antibody was made with GM1, asialo-GM1, GM2, GD1a, and GD1b. Four of the nine patients who developed GBS after being administered gangliosides had IgG anti-GM1(Gc) antibodies. Anti-GM1(Gc) IgG antibody frequencies were higher in patients with GBS after ganglioside therapy than in those who were untreated. Rates of absorption of IgG anti-GM1(Gc) antibodies by GM1 were significantly higher (except for asialo-GM1 and GD1b) than by GM2 and GD1a. The presence of GM1(Gc) was confirmed in bovine brain immunochemically using cholera toxin and Hanganutziu-Deicher antibody. Secondary ion mass spectra showed that the structure of the ganglioside was consistent with that of GM1(Gc). GM1(Gc) was recognized more frequently in sera from patients who developed GBS after ganglioside therapy than in sera from untreated GBS patients. Because N-glycolylneuraminic acid-containing gangliosides seem to be highly immunogenic in humans, GM1(Gc) may act as an immunogen in some patients who develop GBS following ganglioside therapy.

Topics: Animals; Antibody Formation; Cattle; Chromatography, Thin Layer; Cross Reactions; Enzyme-Linked Immunosorbent Assay; G(M1) Ganglioside; Gangliosides; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Mass Spectrometry

Recent work identified anti-GM2 and anti-GalNAc-GD1a IgG ganglioside antibodies as biomarkers in dogs clinically diagnosed with acute canine polyradiculoneuritis, in turn considered a canine equivalent of Guillain-Barré syndrome. This study aims to investigate the serum prevalence of similar antibodies in cats clinically diagnosed with immune-mediated polyneuropathies. The sera from 41 cats clinically diagnosed with immune-mediated polyneuropathies (IPN), 9 cats with other neurological or neuromuscular disorders (ONM) and 46 neurologically normal cats (CTRL) were examined for the presence of IgG antibodies against glycolipids GM1, GM2, GD1a, GD1b, GalNAc-GD1a, GA1, SGPG, LM1, galactocerebroside and sulphatide. A total of 29/41 IPN-cats had either anti-GM2 or anti-GalNAc-GD1a IgG antibodies, with 24/29 cats having both. Direct comparison of anti-GM2 (sensitivity: 70.7%; specificity: 78.2%) and anti-GalNAc-GD1a (sensitivity: 70.7%; specificity: 70.9%) antibodies narrowly showed anti-GM2 IgG antibodies to be the better marker for identifying IPN-cats when compared to the combined ONM and CTRL groups (P = .049). Anti-GA1 and/or anti-sulphatide IgG antibodies were ubiquitously present across all sample groups, whereas antibodies against GM1, GD1a, GD1b, SGPG, LM1 and galactocerebroside were overall only rarely observed. Anti-GM2 and anti-GalNAc-GD1a IgG antibodies may serve as serum biomarkers for immune-mediated polyneuropathies in cats, as previously observed in dogs and humans.

Topics: Animals; Autoantibodies; Biomarkers; Cats; Dogs; G(M1) Ganglioside; G(M2) Ganglioside; Galactosylceramides; Gangliosides; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Polyneuropathies

Guillain-Barré syndrome (GBS) is an acute immune-mediated polyradiculoneuropathy that may follow a preceding infection inducing a cross-reactive antibody response to glycosphingolipids in peripheral nerves. The immune response in GBS is considered to be short lasting, explaining its monophasic clinical course. However, the disease course varies between patients, and residual deficits frequently occur. The duration of the antibody response has not been defined extensively in GBS, and the persistence of these antibodies may impair clinical recovery. The aim of this study was to determine the titer course of serum antibody titers to the ganglioside GM1 in relation to clinical course and outcome in patients with GBS.. Acute-phase sera from patients with GBS included in previous therapeutic trials were screened for anti-GM1 IgG and IgM antibodies in ELISA. Anti-GM1 antibody titers were determined in sera collected at entry and during a 6-month follow-up. Clinical course and outcomes were compared between groups based on the titer course.. Anti-GM1 antibodies were detected in 78 (20.7%) of 377 included patients. The anti-GM1 IgG and IgM antibody titer course was highly variable between patients. A subset of anti-GM1-positive patients had persistent anti-GM1 antibodies at 3 months (n = 27/43 [62.8%]) and 6 months (n = 19/41 [46.3%]). Patients with a high anti-GM1 IgG and IgM titer at entry recovered more slowly and less complete than anti-GM1-negative patients (IgG:. High anti-GM1 IgG and IgM antibody titers at entry and persistent high anti-GM1 IgG antibody titers are associated with poor outcome in patients with GBS. Antibody persistency indicates ongoing antibody production long after the acute disease state in GBS. Further research is required to determine whether antibody persistency interferes with nerve recovery and is a target for treatments.

Topics: Disease Progression; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Immunoglobulin M

Reports suggested an association between SARS-CoV-2 infection and GBS, but subsequent studies produced conflicting results regarding the incidence of GBS during the pandemic. This study assessed positivity rates for GQ1b, GM-1, GD1a, and GD1b for tests performed January 2016, through March 2021, at a national laboratory. Relative to pre-pandemic levels, positivity rates during the pandemic declined by 61% for GQ1b and 24% for GM-1, while unchanged for GD1a and GD1b. These findings suggest heterogeneity with positivity rates of GBS-associated ganglioside antibodies during the COVID-19 pandemic. Mitigation strategies during the pandemic may have reduced the frequency of certain forms of GBS.

Topics: COVID-19; G(M1) Ganglioside; Gangliosides; Guillain-Barre Syndrome; Humans; Pandemics; SARS-CoV-2

In Guillain-Barré syndrome (GBS), both axonal and demyelinating variants can be mediated by complement-fixing anti-GM1 ganglioside autoantibodies that target peripheral nerve axonal and Schwann cell (SC) membranes, respectively. Critically, the extent of axonal degeneration in both variants dictates long-term outcome. The differing pathomechanisms underlying direct axonal injury and the secondary bystander axonal degeneration following SC injury are unresolved. To investigate this, we generated glycosyltransferase-disrupted transgenic mice that express GM1 ganglioside either exclusively in neurons [GalNAcT-/--Tg(neuronal)] or glia [GalNAcT-/--Tg(glial)], thereby allowing anti-GM1 antibodies to solely target GM1 in either axonal or SC membranes, respectively. Myelinated-axon integrity in distal motor nerves was studied in transgenic mice exposed to anti-GM1 antibody and complement in ex vivo and in vivo injury paradigms. Axonal targeting induced catastrophic acute axonal disruption, as expected. When mice with GM1 in SC membranes were targeted, acute disruption of perisynaptic glia and SC membranes at nodes of Ranvier (NoRs) occurred. Following glial injury, axonal disruption at NoRs also developed subacutely, progressing to secondary axonal degeneration. These models differentiate the distinctly different axonopathic pathways under axonal and glial membrane targeting conditions, and provide insights into primary and secondary axonal injury, currently a major unsolved area in GBS research.

Topics: Animals; Autoantibodies; Disease Models, Animal; G(M1) Ganglioside; Gangliosides; Guillain-Barre Syndrome; Mice; Mice, Transgenic; Schwann Cells

We report the case of a 31-year-old man with a finger drop variant of Guillain-Barré syndrome (GBS). The patient visited a neurological clinic with complaints of difficulty in extending the fingers, which occurred seven days after he had fever and diarrhea. The physician who first saw the patient suspected posterior interosseous nerve palsy and referred him to our hospital. Neurological examination 35 days after the onset revealed distal weakness of the upper extremities, particularly in the bilateral extensor digitorum (Medical Research Council [MRC] scale 1/1 [right/left]). The left triceps surae muscle was also weak (MRC scale 5/4). Bilateral Achilles tendon reflexes were absent, but other neurological findings were normal. Cerebrospinal fluid examination showed albuminocytologic dissociation. Serum immunoglobulin G antibodies against GM1 were positive. Nerve conduction studies revealed reduced amplitude of compound muscle action potentials (CMAPs) without evidence of demyelination in the median, ulnar, radial, and tibial nerves. CMAP amplitude was most severely reduced in the radial nerve among the upper extremity nerves. We diagnosed the patient with acute motor axonal neuropathy. His symptoms gradually improved after treatment with intravenous immunoglobulin. When encountering acute finger drop, neurologists should consider the finger drop variant of GBS as a differential diagnosis.

Topics: Adult; Diagnosis, Differential; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Immunoglobulins, Intravenous; Male; Neurologic Examination

Early in life, commensal bacteria play a major role in immune development, helping to guide the host response toward harmful stimuli while tolerating harmless antigens to prevent autoimmunity. Guillain-Barré syndrome (GBS) is an autoimmune disease caused by errant immune attack of antibody-bound ganglioside receptors on host nerve cells, resulting in paralysis. Lipooligosaccharides enveloping the prevalent enteric pathogen, Campylobacter jejuni, frequently mimic human gangliosides and can trigger GBS by stimulating the autoimmune response. In low- to middle-income countries, young children are consistently exposed to C. jejuni, and it is not known if this impacts GBS susceptibility later in life. Using a macrophage model, we examined the effect of training these cells with low doses of ganglioside-mimicking bacteria prior to challenge with GBS-associated antigens. This training caused decreased production of proinflammatory cytokines, suggesting tolerance induction. We then screened Campylobacter isolates from 154 infant fecal samples for GM1 ganglioside mimicry, finding that 23.4% of strains from both symptomatic and asymptomatic infants displayed GM1-like structures. Training macrophages with one of these asymptomatic carrier isolates also induced tolerance against GBS-associated antigens, supporting that children can be exposed to the tolerizing antigen early in life. RNA interference of Toll-like receptor 2 (TLR2) and TLR4 suggests that these receptors are not involved in tolerance associated with decreases in tumor necrosis factor (TNF), interleukin-6 (IL-6), or IL-1β levels. The results of this study suggest that exposure to ganglioside-mimicking bacteria early in life occurs naturally and impacts host susceptibility to GBS development.

Topics: Bacteria; Campylobacter Infections; Campylobacter jejuni; Child; Child, Preschool; G(M1) Ganglioside; Gangliosides; Guillain-Barre Syndrome; Humans; Lipopolysaccharides; Macrophages; Molecular Mimicry; Paralysis

We propose the finger drop sign as a new clinical variant of acute motor axonal neuropathy (AMAN) defined by immunological and radiological evidence. We identified eight consecutive patients who had AMAN. All of them developed prominent involvement of the finger extensors. We performed magnetic resonance imaging (MRI) of the extremity muscles and serological assays for antiganglioside antibodies and Campylobacter jejuni. Patients with AMAN showed characteristic and a markedly sustained weakness of the finger extensors with a distinctive pattern of the finger drop sign. Limb MRI revealed unevenly distributed abnormal signals in the muscles mainly innervated by the posterior interosseous nerve. All tested patients showed positivity for immunoglobulin G antibody against ganglioside complex of GM1 and phosphatidic acid. A pathophysiological understanding of this unique syndrome can provide further insight into antiganglioside-antibody-mediated axonal injury in Guillain-Barré syndrome.

Topics: Aged; Antibodies, Bacterial; Autoantibodies; Axons; Campylobacter jejuni; Electrodiagnosis; Electromyography; Female; Fingers; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Immunoglobulins, Intravenous; Immunologic Factors; Magnetic Resonance Imaging; Male; Middle Aged; Muscle Weakness; Neural Conduction; Neurologic Examination; Phosphatidic Acids; Physical Examination; Retrospective Studies

While children of all ages may be affected by Guillain-Barre-Syndrome (GBS), there are no reports of Dengue Fever (DF) as the preceding or concurrent infection in this age group. In addition, the presence of anti-GM1 IgM antibody, commonly seen in Multifocal Motor Neuropathy, is rarely encountered in both axonal and demyelinating variants of GBS. Moreover, only few neuromuscular ultrasound findings of the axonal variant in children were reported in the literature.. Here we present a nine-year-old female who developed the classic signs, symptoms and neurophysiologic findings of axonal type of GBS during DF. She had elevated anti-GM1 IgM antibody atypical of this variant and diffusely enlarged nerves via neuromuscular ultrasound.. In a pediatric patient with DF and acute flaccid paralysis, GBS should always be one of the considerations. Although rare, anti-ganglioside GM1 IgM antibody can still be found in axonal variant of GBS.

Topics: Antibodies, Anti-Idiotypic; Autoantibodies; Axons; Child; Dengue; Female; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans

We analysed the effect of adding cholesterol to glycolipid antigens on antibody activity with enzyme-linked immunosorbent assay in 123 subjects consisting of 96 patients with Guillain-Barré syndrome, 25 Miller Fisher syndrome, and two Bickerstaff brainstem encephalitis. The use of cholesterol-added GM1 antigens increased anti-GM1 activity in 11 out of 23 anti-GM1-positive patients and resulted in six out of 100 anti-GM1-negative patients becoming anti-GM1-positive. Enhancement of anti-GM1 activity by cholesterol addition was significantly associated with antecedent gastrointestinal infection. The use of cholesterol-added glycolipid antigens can increase the detection rate of anti-glycolipid antibodies and accurately evaluate the anti-glycolipid antibody activity in vivo.

Topics: Autoantibodies; Cholesterol; Encephalitis; Enzyme-Linked Immunosorbent Assay; Female; G(M1) Ganglioside; Glycolipids; Guillain-Barre Syndrome; Humans; Male; Miller Fisher Syndrome; Retrospective Studies

Antibodies against ganglioside complexes (GSCs) are associated with various clinical features and subtypes of Guillain-Barré syndrome (GBS).. One-hundred patients were evaluated for antibodies to GSCs formed by combination of GM1, GM2, GD1a, GD1b, GT1b, and GQ1b using manual enzyme linked immuno-sorbent assay (ELISA).. Twenty-six patients were GSC antibody-positive, most frequent being against GM1-containing GSC (76.9%). Gender distribution, mean age, symptom-duration, antecedent events, electrophysiological subtypes, requirement for mechanical ventilation, and median duration of hospital stay were comparable between the GSC antibody-positive and negative groups. There was no association between specific GSC antibody and electrophysiological subtypes or clinical variants. After controlling for false discovery rate (FDR) using the Benjamini-Hochberg method, the number of subjects who improved in overall disability sum score, modified Erasmus GBS outcome score, and neuropathy symptom score at discharge was significantly higher in the GSC antibody-positive group. Improvements in Medical Research Council sum scores and Hughes Disability Scale during the hospital stay between the GSC antibody-positive and negative groups were not significantly different after controlling for FDR.. The GSC antibody-positive group had better outcome at hospital discharge in some of the disability scores. Pathophysiological pathways among patients without GSC antibodies may be different and this requires further evaluation.

Topics: Adolescent; Adult; Autoantibodies; Case-Control Studies; Cohort Studies; Enzyme-Linked Immunosorbent Assay; Female; G(M1) Ganglioside; G(M2) Ganglioside; Gangliosides; Guillain-Barre Syndrome; Humans; Immunoglobulins, Intravenous; Immunologic Factors; India; Male; Middle Aged; Plasmapheresis; Respiration, Artificial; Time Factors; Treatment Outcome; Young Adult

Approximately 15%-20% of patients with Guillain-Barré syndrome (GBS) are unable to walk independently at 6 months from the onset of neurological symptom. The modified Erasmus GBS outcome score (mEGOS) has been reported as a prognostic tool.Herein we investigated the association between a poor outcome, inability to walk independently at 6 months and presence of antiganglioside antibodies.. The clinical and serological data of 177 patients with GBS were retrospectively collected in Japan to assess the associations between a poor outcome and serum IgG antibodies against each ganglioside (GM1, GD1a, GalNAc-GD1a, GQ1b and GT1a). In addition, we investigated whether the combination of mEGOS and serum IgG antibodies against gangliosides is useful in predicting a poor outcome.. The patients with IgG anti-GD1a antibodies more frequently showed poor outcomes than those without these antibodies (9 (36%) of 25 vs 8 (6%) of 127 patients, p<0.001). Particularly, 80% showed a poor outcome when they had both serum IgG anti-GD1a antibody and a high mEGOS of ≥10 on day 7 of admission.. The combination of serum IgG anti-GD1a antibodies and a high mEGOS could help in making a more accurate prognosis of patients than mEGOS alone, especially for predicting poor outcomes.

Topics: Age Factors; Autoantibodies; Diarrhea; Electrodiagnosis; G(M1) Ganglioside; Gangliosides; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Mobility Limitation; Prognosis; Respiration, Artificial; Retrospective Studies

Topics: Autoantibodies; Autoantigens; Betacoronavirus; Coronavirus Infections; COVID-19; G(M1) Ganglioside; Gangliosides; Guillain-Barre Syndrome; Humans; Male; Middle Aged; Pandemics; Pneumonia, Viral; SARS-CoV-2

Guillain-Barré syndrome, an autoimmune neuropathy characterized by acute limb weakness, is often preceded by

Topics: Complement C1q; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Microscopy, Atomic Force; Protein Binding

Many epidemiological studies of Guillain-Barré syndrome (GBS) and Fisher syndrome (FS) have been conducted in Europe and America. In contrast, epidemiological studies are rare in Asia where the GBS subtypes differ from those in Western countries. This study was undertaken to clarify the incidence of GBS and FS in a local area in Japan as well as their seasonal trends.. Seventy-one GBS and 37 FS patients were recorded from 2006 to 2015 in an area of approximately 1.5 million inhabitants in Japan. The incidence, seasonal trends and clinical features of GBS and FS were examined.. The incidence rate of GBS was 0.42 cases per 100 000 person-years and that of FS was 0.22 cases per 100 000 person-years. The incidence of GBS increased with age and FS affected predominantly patients aged from 45 to 64 years old. There was some seasonal clustering of acute motor axonal neuropathy (AMAN) and FS in spring and summer, but it was not significant. AMAN and FS patients had a high frequency of preceding infection (AMAN, 68% gastrointestinal infection; FS, 65% upper respiratory infection). Antecedent respiratory infection was significantly associated with FS as an outcome. Serum antibodies to ganglioside GM1 were detected in 71% of AMAN patients and antibodies to GQ1b were detected in 81% of FS patients.. Our study offers evidence of a lower incidence of GBS and a higher incidence of FS in a local area in Japan than in Western countries.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Autoantibodies; Child; Child, Preschool; Female; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Incidence; Infant; Japan; Male; Middle Aged; Seasons; Young Adult

Guillain-Barré syndrome (GBS) is an autoimmune disorder of the peripheral nervous system triggered by molecular mimicry between pathogen lipopolysaccharides and host nerve gangliosides. Polymorphisms in the Fas receptor (FAS) and Fas ligand (FASL) genes may potentially alter the elimination of autoreactive immune cells and affect disease susceptibility or disease severity in GBS. We detected single nucleotide polymorphisms (SNPs) in FAS (-1377G/A and -670A/G) and FASL (-843C/T) in a prospective cohort of 300 patients with GBS and 300 healthy controls from the Bangladeshi population. Genotype distributions were not significantly different between patients with GBS and healthy controls. The FAS -670 AG heterozygous (P = 0.0005, OR = 2.5, 95% CI = 1.5-4.2) and GG homozygous (P = 0.0048, OR = 2.6, 95% CI = 1.3-5.0) genotypes were more common in patients with anti-GM1 antibodies than patients without anti-GM1 antibodies. The FAS -670 G allele was more prevalent in anti-GM1 antibody-positive than -negative patients (P = 0.0002, OR = 1.9, 95% CI = 1.4-2.7) and also in patients with the axonal subtype than demyelinating subtype (P < 0.0001, OR = 4.8, 95% CI = 2.3-10.1). The 1377G/-670G GG haplotype was significantly associated with the axonal subtype (P < 0.0001) and anti-ganglioside antibody-positivity (P = 0.0008) in GBS. Serum sFas (237.5 pg/mL vs. 159.5 pg/mL; P < 0.0001) and sFasL (225.1 pg/mL vs. 183.4 pg/mL; P = 0.0069) were elevated in patients with GBS compared to healthy controls, and among patients with high serum sFas was associated with severe GBS (P = 0.0406). In conclusion, this study indicates FAS-FASL promoter SNPs may promote the production of cross-reactive anti-ganglioside antibodies in GBS.

Topics: Adolescent; Adult; Bangladesh; Case-Control Studies; Child; Child, Preschool; Fas Ligand Protein; fas Receptor; Female; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Male; Middle Aged; Peripheral Nervous System; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; Prospective Studies; Young Adult

Previous studies have shown that patients with Guillain-Barré syndrome express autoantibodies against ganglioside GM1 (GM1), although its pathogenic significance for the development of the disease remains to be elucidated. nSMase2 is the best characterized neutral sphingomyelinase (nSMase) found in neuronal cells. Activation of this enzyme leads to ceramide production, which is a known second messenger of the cell-death program in neuronal cells. We have explored the effects of anti-GM1 antibodies on sphingomyelin metabolism of PC12 cells stably transfected with human trk cDNA (PCtrk cells) by determining their effects on nSMase2 activity. The data we present here strongly suggest that anti-GM1 caused a significant change in sphingomyelin content of the membrane fraction in PCtrk cells. Both nSMase2 activity and the level of nSMase2 protein were significantly decreased by anti-GM1 treatment of PCtrk cells, while acidic SMase activities remained unchanged. Our results indicate, for the first time, that anti-GM1 may produce profound impacts on lipid metabolism in neuronal cell membranes.

Topics: Animals; Antibodies; Cell Membrane; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; PC12 Cells; Rats; Sphingomyelin Phosphodiesterase; Sphingomyelins

A 66-year-old man presented with subacute sensorimotor neuropathy in association with small cell lung cancer. Tests for the anti-ganglioside antibody GM1-IgM were positive. Chemotherapy and intravenous immunoglobulin treatment led to a slight improvement in neurological symptoms. Four additional cases of neuropathy accompanied by anti-ganglioside antibody and lung cancer have been reported. The most commonly reported pattern was subacute sensorimotor neuropathy. Patients died from cancer progression after 5 to 18 months. There is evidence that anti-ganglioside antibody inhibits tumor progression, prolonging the patient survival. However, severe neurological disturbance may offset the survival benefit of anti-ganglioside antibody in patients with paraneoplastic neurological syndrome.

Topics: Aged; Autoantibodies; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Immunoglobulins, Intravenous; Immunologic Factors; Lung Neoplasms; Male; Small Cell Lung Carcinoma; Tomography, X-Ray Computed

We describe a twenty-year follow-up study of antiglycolipid antibodies and electrophysiological results in a 36-year-old man with Campylobacter jejuni-associated Guillain-Barré syndrome (GBS). The patient had a high titer of IgG antibodies to GM1 and GA1 20 years ago. Plasma exchange resulted in full recovery from a bedridden status to independent walking in three weeks, except for residual mild weakness of the bilateral extensor hallucis longus muscles and atrophy of the plantar muscles. Twenty years later, he is unable to run at full pace due to neurological sequelae, and IgG antibodies to GM1 and GA1 were still slightly positive. This case suggests that marked improvement in the acute phase does not necessarily guarantee a subsequent good quality of life (QOL). Optional treatment such as complement inhibitors in the acute phase may be required to achieve better QOL in subsets of patients with GBS.

Topics: Adult; Biomarkers; Campylobacter Infections; Campylobacter jejuni; Enteritis; Follow-Up Studies; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Male; Neural Conduction; Plasma Exchange; Prognosis; Quality of Life; Time Factors

Antibodies to the ganglioside GD1b have been reported in various forms of immune-mediated neuropathy, but their clinical relevance for diagnosis and prognosis is unknown. We investigated the prevalence of anti-GD1b antibodies in acute and chronic immune-mediated neuropathies, and the clinical presentation and outcome in Guillain-Barré syndrome (GBS) and Miller Fisher-GBS overlap syndrome (MF-GBS). Anti-GD1b, anti-GM1 and anti-GQ1b antibodies were tested in serum of patients with GBS (N = 165), Miller Fisher syndrome (N = 10), MF-GBS (N = 28), monoclonal gammopathy of unknown significance neuropathy (MGUS; N = 101), chronic inflammatory demyelinating polyneuropathy (N = 29), paraneoplastic syndrome with anti-Hu-associated neuropathy (PNS; N = 11), other auto-immune diseases (AID; N = 60), and healthy controls (HC; N = 60). All samples were tested by enzyme-linked immunosorbent assay according to the Inflammatory Neuropathy Cause and Treatment protocol. IgM anti-GD1b antibodies were found in GBS (N = 4; 2.4%), MGUS (N = 3; 3.0%), and PNS patients (N = 1; 9.1%). IgG anti-GD1b antibodies were found in GBS (N = 20; 12.1%) and MF-GBS (N = 4; 14.3%) patients, but not in the AID and HC group. In the combined group of MF-GBS and GBS patients ((MF-)GBS), 14/36 (38.9%) patients with IgG anti-GD1b antibodies also had IgG anti-GM1 antibodies, and IgG anti-GD1b and IgG anti-GQ1b antibodies were found in 3/29 (10.3%) patients. Patients with (MF-)GBS and anti-GD1b without anti-GM1 antibodies did not differ regarding sensory disturbances or disease severity but recovered faster regarding the ability to walk independently compared with patients without anti-GD1b antibodies (P = 0.031) and with patients with both anti-GD1b and anti-GM1 antibodies (P = 0.034). In conclusion, testing for anti-GD1b antibodies may identify a specific group of immune-mediated neuropathies and (MF-)GBS patients with only anti-GD1b antibodies tend to recover faster.

Topics: Adult; Aged; Autoantibodies; Autoantigens; Autoimmune Diseases of the Nervous System; G(M1) Ganglioside; Gangliosides; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Immunoglobulin M; Lupus Erythematosus, Systemic; Middle Aged; Miller Fisher Syndrome; Monoclonal Gammopathy of Undetermined Significance; Paraneoplastic Polyneuropathy; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; Sjogren's Syndrome

Autoantibodies binding to peripheral nerves followed by complement deposition and membrane attack complex formation results in nerve damage in Guillain-Barré syndrome (GBS). Strategies to remove the pathogenic autoantibodies or block the complement deposition benefit most patients with GBS. Immunoglobulin G-degrading enzyme of Streptococcus pyogenes (IdeS) is a cysteine protease which cleaves IgG antibodies into F(ab')

Topics: Animals; Autoantibodies; Bacterial Proteins; Complement C3; Disease Models, Animal; Disease Progression; Enzyme-Linked Immunosorbent Assay; G(M1) Ganglioside; Guillain-Barre Syndrome; Immunoglobulin G; Neural Conduction; Rabbits; Ranvier's Nodes; Sodium Channels; Statistics, Nonparametric; Time Factors

Elevated titers of serum antibodies against GM1 ganglioside are associated with a variety of autoimmune neuropathies. Much evidence indicates these autoantibodies play a primary role in the disease processes, but the mechanism for their appearance is unclear. We studied the fine specificity of anti-GM1 antibodies of the IgG isotype present in sera from patients with Guillain-Barré syndrome (GBS), using thin-layer chromatogram-immunostaining of GM1, asialo-GM1 (GA1), GD1b and GM1-derivatives with small modifications on the oligosaccharide moiety. We were able to distinguish populations of antibodies with different fine specificity. Remarkably, individual patients presented only one or two of them, and different patients had different populations. This restriction in the variability of antibody populations suggests that the appearance of the anti-GM1 antibodies is a random process involving restricted populations of lymphocytes. With the origin of disease-associated anti-GM1 antibodies as a context, this finding could provide explanation for the "host susceptibility factor" observed in GBS following enteritis with GM1 oligosaccharide-carrying strains of Campylobacter jejuni.

Topics: Adolescent; Adult; Aged; Antibody Specificity; Autoantibodies; Autoimmunity; Child; Cross Reactions; Female; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Male; Middle Aged; Young Adult

Guillain-Barré Syndrome (GBS) is classified into the two major subtypes; acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN). Previous studies have suggested that AIDP is predominant and AMAN is rare in Western countries, whereas AMAN is not always uncommon in East Asia. We aimed to clarify the incidence of the subtypes of GBS in Japan.. We performed a prospective multicentre survey over 3 years (2007-2010). Clinical and electrophysiological findings were collected from 184 patients with GBS in 23 tertiary neurology institutes. Anti-ganglioside antibodies were measured by ELISA. We also surveyed the incidence of Fisher syndrome (FS).. By electrodiagnostic criteria of Ho et al, patients were classified as having AIDP (40%), or AMAN (22%), or unclassified (38%). Anti-GM1 IgG antibodies were found for 47% of AMAN patients, and 18% of AIDP patients (p<0.001). There were no specific regional trends of the electrodiagnosis and anti-GM1 positivity. During the same study period, 79 patients with FS were identified; the percentage of FS cases out of all cases (FS/(GBS+FS)) was 26%.. The frequency of GBS patients with the electrodiagnosis of AMAN by single nerve conduction studies is approximately 20% in Japan, and the AMAN pattern is closely associated with anti-GM1 antibodies. The incidence of FS appears to be much higher in Japan than in Western countries.

Topics: Electrodiagnosis; Female; G(M1) Ganglioside; Gangliosides; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Incidence; Japan; Male; Middle Aged; Miller Fisher Syndrome; Motor Neurons; Neural Conduction; Prospective Studies; Symptom Assessment

Multifocal motor neuropathy (MMN) and the Guillain-Barré syndrome (GBS) are immune-mediated motor neuropathies with antibodies against the ganglioside GM1. In GBS, these antibodies are induced by molecular mimicry, but in MMN their origin is elusive.. We compared the light-chain use of anti-GM1 IgM antibodies in serum from 42 patients with MMN and 23 patients with GBS by ELISA.. Exclusive use of either κ or λ light chains was found in 38 (90%) patients with MMN and 9 (39%) with GBS (p<0.001).. Anti-GM1 IgM antibodies in most patients with MMN are produced by only a single or very limited number of B-cell clones, whereas in most patients with GBS, anti-GM1 IgM antibodies are most likely polyclonal.

Topics: Autoantibodies; B-Lymphocytes; Case-Control Studies; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Immunoglobulin kappa-Chains; Immunoglobulin lambda-Chains; Immunoglobulin M; Polyneuropathies

Topics: Adult; Antibodies, Anti-Idiotypic; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Immunoglobulins, Intravenous; Male

Plasma exchange and intravenous immunoglobulin are effective in treating Guillain-Barré syndrome (GBS) probably because the former removes IgG autoantibodies and complement and the latter inhibits complement activation subsequent to the autoantibody binding to peripheral nerve antigens. IgG degrading enzyme of Streptococcus pyogenes (IdeS) can cleave the pathogenic autoantibodies into F(ab')2 and Fc. The purpose of this study is to show whether IdeS has novel therapeutic potential for GBS. Sera with anti-ganglioside IgG antibodies from 15 patients with GBS or Miller Fisher syndrome were used. We tested whether IdeS cleaved the anti-ganglioside IgG antibodies and inhibited deposition of activated complement component on ELISA plates. IdeS efficiently cleaved IgG and blocked complement activation mediated by anti-GM1, anti-GD1a and anti-GQ1b IgG antibodies. IdeS has therapeutic potential for GBS and related conditions.

Topics: Autoantibodies; Bacterial Proteins; Complement Activation; G(M1) Ganglioside; Gangliosides; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Protein Binding

Sugar chain binding antibodies have gained substantial attention as biomarkers due to their crucial roles in various disorders. In this study, we developed simple and quick detection method of anti-sugar chain antibodies in sera using our previously developed sugar chain-immobilized fluorescent nanoparticles (SFNPs) for the point-of-care diagnostics. Sugar chain structure on SFNPs was modified with the sugar moieties of the GM1 ganglioside via our original linker molecule to detect anti-GM1 antibodies. The structures and densities of the sugar moieties immobilized on the nanoparticles were evaluated in detail using lectins and sera containing anti-GM1 antibodies from patients with Guillain-Barré syndrome, a neurological disorder, as an example of disease involving anti-sugar chain antibodies. When optimized SFNPs were added to sera from patients with Guillain-Barré syndrome, fluorescent aggregates were able to visually detect under UV light in three hours. The sensitivity of the detection method was equivalent to that of the current ELISA method used for the diagnosis of Guillain-Barré syndrome. These results suggest that our method using SFNPs is suitable for the point-of-care diagnostics of diseases involving anti-sugar chain antibodies.

Topics: Antibodies, Immobilized; Autoantibodies; Carbohydrates; Fluorescent Antibody Technique; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Lectins; Nanoparticles; Point-of-Care Systems

A few studies have reported the association of autoantibodies to GM1 or GQ1bα with Alzheimer's disease (AD) or vascular dementia. Here we investigated whether patients with AD or vascular dementia had high titers of the anti-ganglioside antibodies. Sera were obtained from patients with AD (n = 22), vascular dementia (n = 14), Guillain-Barré syndrome, and multifocal motor neuropathy as well as normal controls. Enzyme-linked immunosorbent assay showed titers of IgG and IgM anti-GM1, anti-GQ1bα, and anti-GT1aα antibodies did not differ among AD, vascular dementia, and normal controls, and being remarkably lower than those in Guillain-Barré syndrome and multifocal motor neuropathy. The anti-ganglioside antibodies are not biological markers of AD.

Topics: Adult; Aged; Aged, 80 and over; Alzheimer Disease; Autoantibodies; Biomarkers; Dementia, Vascular; Enzyme-Linked Immunosorbent Assay; Female; G(M1) Ganglioside; Gangliosides; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Immunoglobulin M; Male; Middle Aged; Young Adult

Antibodies to a ganglioside complex consisting of GM1 and GalNAc-GD1a (GM1/GalNAc-GD1a) are found in sera from patients with Guillain-Barré syndrome (GBS). To elucidate the clinical significance of anti-GM1/GalNAc-GD1a antibodies in GBS, clinical features of 58 GBS patients with IgG anti-GM1/GalNAc-GD1a antibodies confirmed by enzyme-linked immunosorbent assay and thin layer chromatography immunostaining were analyzed. Compared to GBS patients without anti-GM1/GalNAc-GD1a antibodies, anti-GM1/GalNAc-GD1a-positive patients more frequently had a preceding respiratory infection (n=38, 66%, p<0.01) and were characterized by infrequency of cranial nerve deficits (n=9, 16%, p<0.01) and sensory disturbances (n=26, 45%, p<0.01). Of the 28 anti-GM1/GalNAc-GD1a-positive patients for whom electrophysiological data were available, 14 had conduction blocks (CBs) at intermediate segments of motor nerves, which were not followed by evident remyelination. Eight of 10 bedridden cases were able to walk independently within one month after the nadir. These results show that the presence of anti-GM1/GalNAc-GD1a antibodies correlated with pure motor GBS characterized by antecedent respiratory infection, fewer cranial nerve deficits, and CBs at intermediate sites of motor nerves. The CB may be generated through alteration of the regulatory function of sodium channels in the nodal axolemma.

Topics: Action Potentials; Adult; Aged; Antibodies; Cranial Nerves; Electric Stimulation; Enzyme-Linked Immunosorbent Assay; Female; G(M1) Ganglioside; Gangliosides; Guillain-Barre Syndrome; Humans; Male; Middle Aged; Neural Conduction; Retrospective Studies; Young Adult

A 51-year-old previously healthy woman presented with Guillain-Barré syndrome (GBS) and elevated liver enzymes. Further diagnostic investigations showed the presence of an acute hepatitis E infection associated with anti-ganglioside GM1 antibodies. After treatment with intravenous immunoglobulins, the patient made a rapid recovery. Here, we report the first case of GBS due to acute hepatitis E virus (HEV) infection associated with the presence of anti-ganglioside GM1 antibodies. We also review available literature on the association between acute HEV infection and GBS.

Topics: Antibodies, Viral; Female; G(M1) Ganglioside; Guillain-Barre Syndrome; Hepatitis E; Hepatitis E virus; Humans; Immunoglobulin G; Immunoglobulin M; Immunoglobulins, Intravenous; Middle Aged; Reverse Transcriptase Polymerase Chain Reaction; Treatment Outcome

It is now emerging the new concept that the antibodies from some patients with Guillain-Barré syndrome (GBS) recognize an antigenic epitope formed by two different gangliosides, a ganglioside complex (GSC). We prepared the dimeric GM1-GD1a hybrid ganglioside derivative that contains two structurally different oligosaccharide chains to mimic the GSC. We use this compound to analyze sera from GBS patients by high-performance thin-layer chromatography immunostaining and enzyme-linked immunosorbent assay. We also synthesized the dimeric GM1-GM1 and GD1a-GD1a compounds that were used in control experiments together with natural gangliosides. The hybrid dimeric GM1-GD1a was specifically recognized by human sera from GBS patients that developed anti-oligosaccharide antibodies specific for grouped complex oligosaccharides, confirming the information that GBS patients developed antibodies against a GSC. High-resolution (1)H-(13)C heteronuclear single-quantum coherence-nuclear overhauser effect spectroscopy nuclear magnetic resonance experiments showed an interaction between the IV Gal-H1 of GM1 and the IV Gal-H2 of GD1a suggesting that the two oligosaccharide chains of the dimeric ganglioside form a single epitope recognized by a single-antibody domain. The availability of a method capable to prepare several hybrid gangliosides, and the availability of simple analytical approaches, opens new perspectives for the understanding and the therapy of several neuropathies.

Topics: Autoantigens; Carbohydrate Conformation; Carbohydrate Sequence; Chromatography, Thin Layer; Enzyme-Linked Immunosorbent Assay; Epitopes; G(M1) Ganglioside; Gangliosides; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Molecular Sequence Data; Oligosaccharides; Oligosaccharides, Branched-Chain; Protein Binding; Serum

Whether or not antiganglioside antibodies are related to axonal or demyelinating Guillain-Barré syndrome (GBS) is still a matter of controversy, as detailed in previous studies conducted in Western and Asian countries.. To clarify whether antiganglioside antibodies are associated with axonal dysfunction in Japanese and Italian GBS patient cohorts.. Clinical and electrophysiological profiles were reviewed for 156 GBS patients collected from Japan (n=103) and Italy (n=53). Serum IgG antibodies against GM1, GM1b, GD1a and GalNAc-GD1a were measured by ELISA in the same laboratory. Electrodiagnostic criteria and results of serial electrophysiological studies were used for classification of GBS subtypes: acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN).. In both Japanese and Italian cohorts, any of the antibodies were positive in 36% of the patients, and antibody positivity had a significant association with the AMAN electrodiagnosis. Approximately 30% of Japanese and Italian antiganglioside positive patients showed the AIDP pattern at the first examination whereas sequential studies showed that most finally showed the AMAN pattern. Clinically, seropositive patients more frequently had preceding diarrhoea and pure motor neuropathy in both Japanese and Italian cohorts; vibratory sensation was normal in 97% of Japanese and in 94% of Italian seropositive patients.. In GBS, clinical and electrophysiological features appear to be determined by antiganglioside antibodies, and the antibodies are associated with motor axonal GBS in both Japan and Italy. Classification of the GBS subtypes as a disease entity should be made, combining the results of antiganglioside assays and serial electrodiagnostic studies.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Autoantibodies; Axons; Child; Electromyography; Enzyme-Linked Immunosorbent Assay; Female; G(M1) Ganglioside; Gangliosides; Guillain-Barre Syndrome; Humans; International Cooperation; Italy; Japan; Male; Middle Aged; Motor Neurons; Neural Conduction; Sensory Receptor Cells; Young Adult

To investigate the relationship of A-waves with conventional electrophysiological subtypes of Guillain-Barré syndrome (GBS), as well as with anti-ganglioside antibodies.. The subjects consisted of 30GBS patients who were classified into acute inflammatory demyelinating polyradiculoneuropathy (AIDP), acute motor axonal neuropathy, and unclassified based on the results of nerve conduction studies. "Abundant A-waves" were defined for the upper-limb nerves (median and ulnar nerves) using receiver-operator characteristic curves. The presence or absence of IgG anti-ganglioside antibodies was also noted.. Abundant A-waves at weeks 3-6 from onset were observed in 64% of the 14 AIDP patients and 0% of 16 non-AIDP patients, and in 60% of 15 antibody-negative patients and 0% of 15 antibody-positive patients. In the earlier period, this relationship was less clear. The correlation between the conventional electrophysiological subtypes and antibodies was present, but was much weaker.. Abundant A-waves in GBS after the acute phase were strongly associated with demyelination that was not mediated by antiganglioside antibodies, possibly through the mechanism of proximal re-excitation induced by electrical inhomogeneities due to segmental demyelination.. Abundant A-waves are promising as a novel reliable marker of demyelination.

Topics: Adult; Aged; Antibodies, Anti-Idiotypic; Brain; Female; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Male; Middle Aged; Neural Conduction; Retrospective Studies; Ulnar Nerve

We describe the case of a 10-year-old child with the acute motor axonal neuropathy (AMAN) form of Guillain-Barré syndrome (GBS) with preserved tendon reflexes, 6 days after a bout of gastroenteritis. The child quickly showed weakness of the distal muscles of his four limbs, with preserved tendon reflexes and a raised CSF protein concentration with no cells. Nerve conduction studies showing motor axonal degeneration confirmed the diagnosis of GBS in spite of preserved tendon reflexes. The serum was positive for IgG antibodies to gangliosides GM1 and GD1b. The child received intravenous immunoglobulins, which resulted in a favorable progression. This case proves that GBS with normal tendon reflexes exists. The other cases of SGB with preserved tendon reflexes already described in the literature were the AMANs form with antibodies to gangliosides in the serum and only adults were affected.

Topics: Axons; Biomarkers; Child; Follow-Up Studies; G(M1) Ganglioside; Gangliosides; Gastroenteritis; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Immunoglobulins, Intravenous; Male; Muscle Weakness; Reflex, Stretch; Treatment Outcome

In the Guillain-Barré syndrome subform acute motor axonal neuropathy (AMAN), Campylobacter jejuni enteritis triggers the production of anti-ganglioside Abs (AGAbs), leading to immune-mediated injury of distal motor nerves. An important question has been whether injury to the presynaptic neuron at the neuromuscular junction is a major factor in AMAN. Although disease modeling in mice exposed to AGAbs indicates that complement-mediated necrosis occurs extensively in the presynaptic axons, evidence in humans is more limited, in comparison to the extensive injury seen at nodes of Ranvier. We considered that rapid AGAb uptake at the motor nerve terminal membrane might attenuate complement-mediated injury. We found that PC12 rat neuronal cells rapidly internalized AGAb, which were trafficked to recycling endosomes and lysosomes. Consequently, complement-mediated cytotoxicity was attenuated. Importantly, we observed the same AGAb endocytosis and protection from cytotoxicity in live mouse nerve terminals. AGAb uptake was attenuated following membrane cholesterol depletion in vitro and ex vivo, indicating that this process may be dependent upon cholesterol-enriched microdomains. In contrast, we observed minimal AGAb uptake at nodes of Ranvier, and this structure thus remained vulnerable to complement-mediated injury. These results indicate that differential endocytic processing of AGAbs by different neuronal and glial membranes might be an important modulator of site-specific injury in acute AGAb-mediated Guillain-Barré syndrome subforms and their chronic counterparts.

Topics: Animals; Antibodies, Anti-Idiotypic; Complement Activation; Disease Models, Animal; Endocytosis; Female; G(M1) Ganglioside; Gangliosides; Guillain-Barre Syndrome; Male; Mice; Mice, Inbred C57BL; Motor Neurons; Neuromuscular Junction; PC12 Cells; Ranvier's Nodes; Rats

Our aim was to investigate the in vivo gene expression pattern of the Guillain-Barre syndrome (GBS) with DNA microarrays and bioinformatics tools. Oral-infusion model animals mimicking human infection of GBS were analyzed. Tissue samples and body fluids were collected to perform antibody tests and biopsy assays. Gene-expression microarray was conducted with nerve tissues and GBS-related genes were elucidated via bioinformatics tools. Model animals showed typical symptoms of GBS in that mild demyelination was shown by cerebellar white matter and by lumbar enlargement of model animals. Then, 81.25% of the model animals were positive with GM1-IgG antibodies by ELISA. In the microarray analysis, 1,261 genes were identified with statistically different expression (P < 0.05), 21 of which were associated with gene function analysis, gene pathway identification, signal transduction and co-expression network construction. Furthermore, quantitative PCR was used to characterize the gene expression level. We found that genes of HPRT1, PKC and PPARGC-1 were in the core of the network, while the expression of PPARGC-1, SUS2DD and AMPKA2 were significantly inhibited. A total of 21 genes were found to be actively involved in the process of protein transportation, transcriptional regulation, antigen identification and cell cycle regulation during the GBS infection period. The co-expression network indicated an important association between GBS and the 21 genes, especially the down-regulated ones. In conclusion, we demonstrated that GBS-affected hosts had a specific gene expression profile, which may guide the direction of GBS research and therapy.

Topics: Animals; Antibodies; Biopsy; Campylobacter jejuni; Female; G(M1) Ganglioside; Gene Expression Profiling; Gene Expression Regulation; Gene Regulatory Networks; Guillain-Barre Syndrome; Humans; Immunoassay; Immunoglobulin G; Male; Oligonucleotide Array Sequence Analysis; Reproducibility of Results; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Staining and Labeling; Swine; Swine Diseases; Swine, Miniature

Immunization of rabbits with bovine brain gangliosides induced an experimental neuropathy, with clinical signs resembling Guillain-Barré syndrome. All the immunized animals developed immunoglobulin G immunoreactivity to GM1 ganglioside. In a few (4 of 27) animals, an additional anti-ganglioside antibody population showing an unusual binding behavior was detected. Enzyme-linked immunosorbent assay and thin-layer chromatography immunostaining analyses showed that the binding of these unusual antibodies required the presence of two co-localized gangliosides. Maximal interaction was observed to a mixture of GM1 and GD1b, but the antibodies also showed "density-dependent" binding to GD1b. The antibodies were purified by affinity chromatography and displayed the ability to target antigens in biological membranes (rat synaptosomes).

Topics: Animals; Brain Chemistry; Cattle; G(M1) Ganglioside; Gangliosides; Guillain-Barre Syndrome; Immunoglobulin G; Neuritis, Autoimmune, Experimental; Rabbits; Rats

Previous studies have shown that anti-GQ1b antibodies induce massive neuromuscular blocking. If anti-GM1 and -GD1a antibodies have similar effects on the neuromuscular junction (NMJ) in human limb muscles, this may explain selective motor involvement in axonal Guillain--Barré syndrome (GBS).. Axonal-stimulating single-fibre electromyography was performed in the extensor digitorum communis muscle of 23 patients with GBS, including 13 with the axonal form whose sera had a high titre of serum IgG anti-GM1 or -GD1a antibodies.. All patients with axonal or demyelinating GBS showed normal or near-normal jitter, and no blocking.. In both axonal and demyelinating GBS, neuromuscular transmission is not impaired. Our results failed to support the hypothesis that anti-GM1 or -GD1a antibody affects the NMJ. In GBS, impulse transmission is presumably impaired in the motor nerve terminal axons proximal to the NMJ.

Topics: Adult; Aged; Autoantibodies; Axons; Electromyography; Female; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Male; Middle Aged; Muscle, Skeletal; Neuromuscular Junction; Synaptic Transmission; Young Adult

Carbohydrate mimicry between Campylobacter jejuni lipooligosaccharides (LOS) and host neural gangliosides plays a crucial role in the pathogenesis of Guillain-Barré syndrome (GBS). Campylobacter jejuni LOS may mimic various gangliosides, which affects the immunogenicity and the type of neurological deficits in GBS patients. Previous studies have shown the interaction of LOS with sialic acid-specific siglec receptors, although the functional consequences remain unknown. Cells that express high levels of siglecs include dendritic cells (DCs), which are crucial for initiation and differentiation of immune responses. We confirm that α2,3-sialylated GD1a/GM1a mimic and α2,8-sialylated GD1c mimic LOS structures interact with recombinant Sn and siglec-7, respectively. Although the linkage of the terminal sialic acid of LOS did not regulate expression of DC maturation markers, it displayed clear opposite expression levels of interleukin-12 (IL-12) and OX40L, molecules involved in DC-mediated Th cell differentiation. Accordingly, targeting DC-expressed siglec-7 with α2,8-linked sialylated LOS resulted in Th1 responses, whereas Th2 responses were induced by targeting with LOS containing α2,3-linked sialic acid. Thus, our data demonstrate for the first time that depending on the sialylated composition of Campylobacter jejuni LOS, specific Th differentiation programs are initiated, possibly through targeting of distinct DC-expressed siglecs.

Topics: Campylobacter jejuni; Carbohydrate Conformation; Cell Differentiation; Cell Line; Cell Polarity; Dendritic Cells; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; G(M1) Ganglioside; Gangliosides; Guillain-Barre Syndrome; HEK293 Cells; Humans; Interleukin-12; Lectins; Lipopolysaccharides; Molecular Mimicry; N-Acetylneuraminic Acid; OX40 Ligand; Polymerase Chain Reaction; Sialic Acid Binding Immunoglobulin-like Lectins; T-Lymphocytes; Th1 Cells; Th2 Cells

Topics: Antibodies, Antiphospholipid; Axons; Biomarkers; Campylobacter Infections; Campylobacter jejuni; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Lipopolysaccharides; Molecular Mimicry; Myelin Sheath; Neuromuscular Junction; Ranvier's Nodes

Guillain-Barré syndrome (GBS) is an autoimmune disorder affecting the peripheral nervous system, usually triggered by an acute infection. GBS patients are known to have antecedent bacterial infections associated with auto-antibodies to various gangliosides. This investigation aimed to evaluate GBS patients for serological evidence of Mycoplasma pneumoniae infection and anti GM1 ganglioside antibodies.. This cross-sectional study included 57 pediatric GBS patients, 42 neurological controls (i.e., non-GBS Acute Flaccid Paralysis cases) and 35 non-neurological controls. Enzyme linked immune sorbent assay (ELISA) was performed on the sera of the subjects to detect IgM and IgG antibodies against Mycoplasma (M.) pneumoniae and GM1 gangliosides.. The results showed that 15.79% and 21.05% GBS patients were positive for IgG and IgM antibodies against M. pneumoniae as compared to 2.38% (P < 0.05) and 14.2% in non-GBS-AFP and 5.7% and 14.2% in non-neurological controls respectively. Additionally, 43.85% and 38.54% GBS patients were positive for IgG and IgM antibodies against GM1 gangliosides as compared to 38.09% and 28.57% in non-GBS-AFP and 14.2% and 2.84% in non-neurological controls respectively (P < 0.05).. Significant difference in levels of IgG antibodies against M. pneumoniae was observed between GBS patients and neurological controls, suggesting M. pneumoniae to be an important antecedent to GBS. Significant difference in levels of anti GM1 ganglioside antibodies (IgG & IgM) was seen between GBS patients and non-neurological controls, highlighting its possible role in the pathogenesis of GBS.

Topics: Antibodies, Bacterial; Autoantibodies; Child; Child, Preschool; Cross-Sectional Studies; Enzyme-Linked Immunosorbent Assay; Female; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Immunoglobulin M; Male; Pneumonia, Mycoplasma; Prevalence

Antibodies to the ganglioside GM1 are associated with various forms of acute and chronic immune-mediated neuropathy, including Guillain-Barré syndrome (GBS) and multifocal motor neuropathy. In diagnostics and research, these antibodies are usually detected by GM1 preparations derived from bovine brain tissue, which are non-covalently attached to solid carriers such as enzyme-linked immunosorbent assay (ELISA) plates. Such brain-derived GM1 preparations are potentially contaminated with other glycolipids. In the current study, uncontaminated mono- and divalent synthetic analogs of the ganglioside GM1 were successfully attached via covalent bonds onto the surface of ELISA plates. The resulting modified diagnostic tool showed strong affinities and good specificities for binding of monoclonal mouse and human anti-GM1 antibodies and cholera toxin, as well as for the anti-GM1 antibodies in serum samples from neuropathy patients. While these proof-of-principle experiments reveal the potential of synthetic ganglioside mimics in diagnostics, they show the necessity of further studies to overcome certain limitations, specifically the non-specific interactions in the negative control assays with synthetic GM1.

Topics: Antibodies, Monoclonal; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Molecular Mimicry; Paraproteinemias; Polyneuropathies

Campylobacter jejuni enteritis is frequently associated with an axonal form of Guillain-Barré syndrome (GBS) and C. jejuni DNA-binding protein from starved cells (C-Dps) induces paranodal myelin detachment and axonal degeneration through binding with sulfatide in vivo. Here we investigated the invasion of C-Dps into hosts with C. jejuni-related GBS. Our analyses of patient sera found that both C-Dps and anti-C-Dps antibodies were most commonly detected in sera from C. jejuni-related GBS patients (5/27, 14.8% and 15/24, 62.5%; respectively). These findings suggest that C-Dps invades the host and may potentially contribute to the peripheral nerve damage in C. jejuni-related GBS.

Topics: Adolescent; Adult; Aged; Bacterial Proteins; Campylobacter jejuni; Child; DNA-Binding Proteins; Female; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Male; Middle Aged; Young Adult

Guillain-Barré syndrome sometimes manifests as immune reconstitution inflammatory syndrome. We report a treatment-naïve male with chronic HIV-1 infection who presented with an axonal variant of Guillain-Barré syndrome. Antiretroviral therapy commenced one month later and no rapid improvement or deterioration of tetraparesis was noted. This is the first report that describes the detection and serial measurements of anti-ganglioside antibody in a patient with HIV infection. This case suggests a limited role for T-cell immunity in the production of anti-ganglioside antibody and the pathogenesis of axonal variants, since the antiretroviral therapy-induced improvement in T-cell immunity neither re-elevated anti-ganglioside antibody titer nor worsened tetraparesis.

Topics: Adult; Anti-Retroviral Agents; G(M1) Ganglioside; Guillain-Barre Syndrome; HIV Infections; HIV-1; Humans; Immunoglobulin G; Male

Clinical severity of Guillain-Barré syndrome (GBS) is highly variable, but the immunopathological reason is unknown.. The study was designed to show which antibody parameters are associated with disease severity in GBS patients with serum anti-GM1 IgG antibodies.. Thirty-four GBS patients with anti-GM(1) IgG antibodies were grouped into two categories according to disease severity at nadir: mild (grades 1-3 by Hughes functional scale, n=13) and severe (grades 4 and 5, n=21). Titre, affinity, fine specificity and cell binding of anti-GM(1) antibodies were obtained and compared between the two groups.. No differences in antibody titre (GM(1)-ELISA) or affinity were found between the two patient groups. In contrast, the severe group showed a significantly higher frequency (95%, vs 46% in the mild group, p=0.002) of specific (not cross-reacting with GD(1b)) anti-GM(1) antibodies. In addition, the severe group also exhibited a higher antibody binding titre to cellular GM(1).. Differences in fine specificity of antibodies are strong indications that different regions of the GM(1)-oligosaccharide are involved in antibody binding. High titres of specific anti-GM(1) antibody binding to cellular GM(1) can be explained by antigen exposure, that is, GM(1) exposes or forms mainly epitopes recognised by specific antibodies, and 'hides' those involved in binding of cross-reacting antibodies. Thus, the fine specificity of anti-GM(1) antibodies may influence disease severity by affecting antibody binding to cellular targets. Additionally, since antibody specificity studies are relatively easy to implement, fine specificity could be considered a useful predictor of disease severity.

Topics: Adolescent; Adult; Aged; Autoantibodies; Child; Child, Preschool; Chromatography, Thin Layer; Disability Evaluation; Enzyme-Linked Immunosorbent Assay; Female; G(M1) Ganglioside; Gangliosides; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Male; Middle Aged; Severity of Illness Index; Surveys and Questionnaires; Young Adult

Guillain-Barré syndrome (GBS) is an acquired demyelinating neuropathy, characterized by infiltration of peripheral nerves with macrophages and T cells. There have been reports of antibodies to glycolipids in GBS. We have previously found T cell reactivity to glycolipids in patients with the demyelinating form of GBS. This study was performed to characterize the cytokines produced by these T cells. Peripheral blood lymphocytes from patients with GBS, chronic inflammatory demyelinating polyradiculoneuropathy, healthy control patients and other neuropathies were incubated with the ganglioside GM1 and transferred to enzyme-linked immunospot plates. The average number per well of spot-forming cells (SFC) in the absence of antigen was counted. The average spontaneous SFC number was subtracted from the average SFC number in the presence of GM1, to produce a corrected SFC. There was significantly increased production of interferon-gamma but not interleukin-5 in response to stimulation with the ganglioside GM1. This could indicate that SFC have a role in pathogenesis of disease.

Topics: Cells, Cultured; Enzyme-Linked Immunosorbent Assay; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Interferon-gamma; Interleukin-5; T-Lymphocytes

Anti-ganglioside antibodies with a pathogenic potential are present in C. jejuni-associated Guillain-Barré syndrome (GBS) patients and are probably induced by molecular mimicry. Immunization studies in rabbits and mice have demonstrated that these anti-ganglioside antibodies can be induced using purified lipo-oligosaccharides (LOS) from C. jejuni in a strong adjuvant.. To investigate whether natural colonization of chickens with a ganglioside-mimicking C. jejuni strain induces an anti-ganglioside response, and to investigate the diversity in anti-ganglioside response between and within genetically different chicken lines, we orally challenged chickens with different C. jejuni strains. Oral challenge of chickens with a C. jejuni strain from a GBS patient, containing a LOS that mimics ganglioside GM1, induced specific IgM and IgG anti-LOS and anti-GM1 antibodies. Inoculation of chickens with the Penner HS:3 serostrain, without a GM1-like structure, induced anti-LOS but no anti-ganglioside antibodies. We observed different patterns of anti-LOS/ganglioside response between and within the five strains of chickens.. Natural infection of chickens with C. jejuni induces anti-ganglioside antibodies. The production of antibodies is governed by both microbial and host factors.

Topics: Adjuvants, Immunologic; Animals; Campylobacter jejuni; Chickens; G(M1) Ganglioside; Guillain-Barre Syndrome; Immunization; Immunoglobulin G; Kinetics; Lipopolysaccharides; Mice; Molecular Mimicry; Rabbits; Species Specificity

From June to July 2007, 36 cases of Guillain-Barre syndrome (GBS) occurred in a township in north China. Serological study and bacteria culture were performed to investigate the association between preceding Campylobacter jejuni infection and this GBS outbreak. Anti-C. jejuni antibodies were found in significantly higher numbers of GBS patients (IgM 84%, IgG 87.5%) than in healthy inspection cases (IgM 33%, IgG 27%). IgG anti-GM1 was the dominant anti-ganglioside antibody among the GBS patients. Seven C. jejuni isolates (four from human stool and three from poultry specimens taken from the patients' houses) were obtained. Serotyping and molecular analysis were used to investigate the genetic relatedness among these C. jejuni isolates. The four human isolates, collected from residents of the same district, were indistinguishable by both pulsed-field gel electrophoresis and multilocus sequence typing, suggesting these patients had a common source of infection. A new sequence type, sequence type-2993, was assigned to the human C. jejuni isolates, three of which belonged to Penner serotype heat-stable (HS):41. Both serotype and molecular subtype of the human C. jejuni isolates were different from those of isolates obtained from poultry specimens. Our results suggest that the antecedent C. jejuni infection triggered this GBS outbreak in China.

Topics: Adult; Animals; Anti-Bacterial Agents; Antibodies, Bacterial; Campylobacter Infections; Campylobacter jejuni; Chickens; China; Disease Outbreaks; Feces; Female; Food Microbiology; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Male; Meat; Microbial Sensitivity Tests; Retrospective Studies; Serotyping; Young Adult

Topics: Female; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Middle Aged; Motor Neurons; Muscle Weakness; Neural Conduction; Neurologic Examination; Pyramidal Tracts; Reflex, Babinski

Previous studies have shown that patients with the axonal form of Guillain-Barré syndrome (GBS) develop autoantibodies against GM1 ganglioside (GM1). Nerve growth factor (NGF) is essential for neuronal survival in vivo and its functional receptor is Trk-tyrosine kinase. Here, we examined the biological effects of sera from patients with the axonal form of GBS on the morphology and the phosphorylation state of Trk-tyrosine kinase in PC12 cells. Furthermore, we examined the effect of the sera on the integrity of membrane lipid rafts biochemically. The data show that anti-GM1 antibodies found in patients' sera but not control sera inhibit NGF-induced Trk autophosphorylation. Most intriguingly, the autoantibodies alter the distribution of Trk in lipid rafts without shifting the distribution of a rafts marker protein. These data strongly suggest that anti-GM1 antibodies directly influence the integrity of the signaling platform, lipid rafts, implicating the importance of lipid rafts in the development of this disorder.

Topics: Adult; Aged; Animals; Autoantibodies; Blotting, Western; Cell Line; Female; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Immunoprecipitation; Male; Membrane Microdomains; Middle Aged; Nerve Growth Factor; PC12 Cells; Phosphorylation; Rats; Receptor, trkA; Young Adult

Topics: Autoantibodies; Biomarkers; Enzyme-Linked Immunosorbent Assay; G(M1) Ganglioside; Gangliosides; Guillain-Barre Syndrome; Humans; Miller Fisher Syndrome; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; Specimen Handling

To determine the epitopes of ganglioside complexes (GSCs) containing GQ1b or GT1a, we investigated their reactivity to GSCs consisting of asialo-GM1 (GA1) and GQ1b or GT1a using IgG anti-GQ1b- or anti-GT1a-positive sera. Nine anti-GQ1b-positive sera had higher activity to GA1/GQ1b than to GQ1b, only five of which reacted with GM1/GQ1b and GD1b/GQ1b. Five of 14 sera positive for GA1/GT1a and GM1/GT1a were negative for GA1/GQ1b and GM1/GQ1b. Sialic acids attached to the internal galactose of gangliotetraose can influence the reactivity of anti-GSC antibodies. Screening for antibodies to GSCs containing GA1 is useful for elucidation of the antibody-mediated pathophysiology.

Topics: Antibodies, Monoclonal; Autoantibodies; Enzyme-Linked Immunosorbent Assay; G(M1) Ganglioside; Gangliosides; Guillain-Barre Syndrome; Humans; Miller Fisher Syndrome

We report the case of a patient with Parkinson's disease who developed rapidly progressive weakness of the four limbs due to an acute motor axonal neuropathy (AMAN). This occurred days after a neuroleptic malignant syndrome (NMS). Serologic evidence of a preceding Campylobacter jejuni infection was detected and treatment with intravenous immunoglobulins proved effective. This case suggests that the rarely described neuropathies occurring with NMS may have a postinfectious immune basis and respond to immunomodulatory therapy.

Topics: Antibodies, Bacterial; Antiparkinson Agents; Campylobacter Infections; Campylobacter jejuni; Electromyography; Fever; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Immunoglobulin M; Immunoglobulins, Intravenous; Lipopolysaccharides; Male; Middle Aged; Molecular Mimicry; Neural Conduction; Neuroleptic Malignant Syndrome; Parkinson Disease; Quadriplegia; Unconsciousness

Gangliosides are glycolipids mainly present at the plasma membrane (PM). Antibodies to gangliosides have been associated with a wide range of neuropathy syndromes. Particularly, antibodies to GM1 ganglioside are present in patients with Guillain-Barré syndrome (GBS). We investigated the binding and intracellular fate of antibody to GM1 obtained from rabbits with experimental GBS in comparison with the transport of cholera toxin (CTx), which binds with high affinity to GM1. We demonstrated that antibody to GM1 is rapidly and specifically endocytosed in CHO-K1 cells. After internalization, the antibody transited sorting endosomes to accumulate at the recycling endosome. Endocytosed antibody to GM1 is recycled back to the PM and released into the culture medium. In CHO-K1 cells, antibody to GM1 colocalized with co-endocytosed CTx at early and recycling endosomes, but not in Golgi complex and endoplasmic reticulum, where CTx was also located. Antibody to GM1, in contraposition to CTx, showed a reduced internalization to recycling endosomes in COS-7 cells and neural cell lines SH-SY5Y and Neuro2A. Results from photobleaching studies revealed differences in the lateral mobility of antibody to GM1 in the PM of analyzed cell lines, suggesting a relationship between the efficiency of endocytosis and lateral mobility of GM1 at the PM. Taken together, results indicate that two different ligands of GM1 ganglioside (antibody and CTx) are differentially endocytosed and trafficked, providing the basis to gain further insight into the mechanisms that operate in the intracellular trafficking of glycosphingolipid-binding toxins and pathological effects of neuropathy-associated antibodies.

Topics: Animals; Autoantibodies; Chlorocebus aethiops; CHO Cells; Cholera Toxin; COS Cells; Cricetinae; Cricetulus; Endocytosis; Epithelial Cells; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Protein Transport; Rabbits; Transport Vesicles

A 38-year-old man presented with distal-dominant limb weakness two weeks after an upper respiratory infection. He had no sensory and autonomic signs and no cranial nerve involvement during the course of the disease. Tendon reflexes were preserved except for an absent Achilles' tendon reflex. His disability at nadir was grade 2 on the Hughes functional scale. Cerebrospinal fluid analysis showed albuminocytologic dissociation and he was diagnosed with pure motor Guillain-Barré syndrome (GBS). Thin-layer chromatography immunostaining and an enzyme-linked immunosorbent assay revealed an immunoglobulin G antibody to the ganglioside complex GM1/GalNAc-GD1a in his acute phase serum. A serial nerve conduction study revealed conduction block in the median and ulnar nerve trunks and temporal dispersion in the tibial nerve, without an evident remyelination pattern during the course of the disease. A sensory nerve conduction study was normal. According to Hadden's criteria, the electrodiagnostic findings were judged as a primary demyelinating pattern. Weakness and abnormal motor nerve conduction recovered rapidly after intravenous immunoglobulin therapy. In view of the localization of GM1 and GalNAc-GD1a on the axolemma of the motor nerves, the clinical course and electrophysiological features may have resulted from functional conduction failure at the nodes of Ranvier of the motor nerves, rather than primary demyelination or axonal degeneration. The illness resembled acute motor conduction block neuropathy characterized by preserved sensory function, an early conduction block at intermediate nerve segments, and good recovery. GM1 and GalNAc-GD1a may form a complex in the axolemma at the nodes of Ranvier or paranodes of the motor nerves, and may be a target antigen in pure motor GBS; especially in the form with acute motor conduction block neuropathy. The present case is the first description of a GBS patient with an IgG anti-GM1/GalNAc-GD1a antibody.

Topics: Autoantibodies; G(M1) Ganglioside; Gangliosides; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Male; Motor Neuron Disease; Neural Conduction

GM1 and GalNAc-GD1a are located on the axolemma of the motor nerves and are believed to be the antigens associated with pure motor Guillain-Barré syndrome (GBS). Furthermore, GM1 and GalNAc-GD1a may exist nearby and colocalize on the axolemma. Ganglioside complex (GSC) antigens associated with GM1 or GalNAc-GD1a can be target antigens in pure motor GBS. We investigated GBS sera for antibodies to a GSC consisting of GM1 and GalNAc-GD1a (GM1/GalNAc-GD1a) and analyzed the clinical and electrophysiologic findings of patients with antibodies to GM1/GalNAc-GD1a.. Sera from 224 patients with GBS were surveyed for antibodies to GSCs consisting of two of nine gangliosides (GM1, GM2, GM3, GD1a, GD3, GT1a, GT1b, GQ1b, and GalNAc-GD1a). We analyzed the clinical and electrophysiologic features of patients with IgG antibodies to the GM1/GalNAc-GD1a complex.. Ten patients with GBS had IgG antibodies to the GM1/GalNAc-GD1a complex. The clinical findings of the 10 patients with GBS were characterized by preserved sensory system and infrequent cranial nerve deficits. According to the criteria established by Hadden et al., electrodiagnostic studies showed a demyelinating pattern in four patients and axonal neuropathy pattern in two. Early motor conduction block at intermediate nerve segments was found in five patients.. GM1 and GalNAc-GD1a may form a complex in the axolemma at nodes of Ranvier or paranodes of the motor nerves, and may be a target antigen in pure motor Guillain-Barré syndrome, especially in the form of acute motor conduction block neuropathy.

Topics: Action Potentials; Adult; Aged; Chromatography, Thin Layer; Enzyme-Linked Immunosorbent Assay; Female; G(M1) Ganglioside; Gangliosides; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Male; Middle Aged; Neural Conduction; Retrospective Studies; Young Adult

CD1 molecules present a variety of microbial glycolipids and self-glycolipids to T cells, but their potential role in humoral responses to glycolipid Ags remains to be established. To address this issue directly, we used GM1/GD1a-deficient mice, which, upon immunization with heat-killed Campylobacter jejuni, develop Guillain-Barré syndrome-associated IgG Abs against the GM1/GD1a sugar chain epitopes of bacterial lipo-oligosaccharides (LOS). Our results showed that anti-ganglioside Abs of the IgG1, IgG2b, and IgG3 isotypes were produced in the absence of group 2 CD1 (CD1d) expression. Unlike mouse and human group 2 CD1 molecules that specifically bound LOS, none of the group 1 CD1 molecules (CD1a, CD1b, and CD1c in humans) were capable of interacting with LOS. Thus, these results indicate CD1-independent pathways for anti-ganglioside Ab production.

Topics: Animals; Antibodies; Antibody Formation; Antigens, CD1; Campylobacter jejuni; G(M1) Ganglioside; Gangliosides; Guillain-Barre Syndrome; Immunoglobulin G; Lipopolysaccharides; Mice; Mice, Mutant Strains

Antiganglioside antibodies have been reported to play a part in the pathophysiology of Guillain-Barré syndrome (GBS).. To investigate the prevalence and correlation of anti-ganglioside antibodies with clinical data in children with GBS in a multicentre clinical trial.. Immunoglobin (Ig)G and IgM to GM1, GM1b, GD1a, GalNAc-GD1a, GD1b, GT1a, and GQ1b were measured by ELISA in sera obtained before treatment. In addition, serological testing for Campylobacter jejuni was carried out. In parallel, a group of adults with GBS and a control group of children without GBS or other inflammatory diseases were evaluated.. Sera from 63 children with GBS, 36 adults with GBS and 41 children without GBS were evaluated. Four of the children with GBS showed positive IgG to GM1, in one case combined with anti-GalNAc-GD1a and in one with anti-GD1b. Two others showed isolated positive IgG to GD1b and GT1a. One showed increased anti-GalNAc-GD1a IgM. In 5 of the 63 children, serological evidence of a recent infection with C jejuni was found, and this correlated significantly with the raised antibodies (p = 0.001). In the control group without GBS, no child showed positive IgG, but one showed anti-GalNAc-GD1a IgM. Compared with the adults with GBS, the frequency of antibodies in children was insignificantly lower. In our study, patients with positive antibodies did not show a more severe GBS course or worse outcome than those who were seronegative, and we could not show an increased incidence of axonal dysfunction.. In some children with GBS, one can detect raised IgG against various gangliosides, similar to that in adults. A recent infection with C jejuni is markedly associated with the presence of these antibodies. However, in contrast with what has been reported in adults, in this study we were unable to show a negative effect of these findings on the clinical course.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Campylobacter Infections; Campylobacter jejuni; Child; Child, Preschool; Enzyme-Linked Immunosorbent Assay; Female; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Immunoglobulin M; Infant; Male; Middle Aged; Prospective Studies

Ganglioside complexes (GSCs) are known as target antigens in Guillain-Barré syndrome (GBS). To elucidate the clinical importance of the anti-GSC antibodies in GBS, we investigated serum antibodies to GSCs containing two of the gangliosides, GM1, GD1a, GD1b and GT1b, and analyzed clinical features of anti-GSC-positive GBS patients. Thirty-nine (17%) of 234 GBS patients had IgG anti-GSC antibodies. Anti-GSC-positive GBS had antecedent gastrointestinal infection and lower cranial nerve deficits more frequently than control GBS. The presence of antibody specificity to GD1a/GD1b and/or GD1b/GT1b was significantly associated with severe disability and a requirement for mechanical ventilation.

Topics: Adult; Autoantibodies; Campylobacter Infections; Campylobacter jejuni; Cranial Nerve Diseases; Disability Evaluation; Electrophysiology; Female; G(M1) Ganglioside; Gangliosides; Gastrointestinal Diseases; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Immunosorbent Techniques; Male; Middle Aged; Respiration, Artificial; Severity of Illness Index

The capacity of ganglioside-specific autoantibodies to recruit leukocyte effector functions was studied. Serum samples from 87 patients with Guillain-Barré (GBS) or Miller Fisher syndrome (MFS), containing GM1-, GQ1b-, or GD1b-specific IgG or IgA, were tested for leukocyte activating capacity. Ganglioside-specific IgG antibodies generally induced leukocyte activation, irrespective of specificity. The magnitude of leukocyte degranulation correlated with GM1- and GQ1b-specific IgG titers, but not with disease severity. Finally, GM1-specific IgA activated leukocytes through the IgA receptor, FcalphaRI (CD89). Therefore, both ganglioside-specific IgG and IgA can recruit leukocyte effector functions, which may be relevant in the pathogenesis of GBS and MFS.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antibody Specificity; Antigens, CD; Autoantibodies; Cell Degranulation; Child; Child, Preschool; Female; G(M1) Ganglioside; Gangliosides; Guillain-Barre Syndrome; Humans; Immunoglobulin A; Immunoglobulin G; Leukocytes; Male; Middle Aged; Miller Fisher Syndrome; Receptors, Fc

To reveal the biological and pathological roles of anti-GM1 antibody in Guillain-Barré syndrome (GBS), we examined its effects on nerve growth factor (NGF) induced TrkA autophosphorylation (NGF-TrkA signaling) in PC12 cells, a sympathetic nerve cell line. The NGF-TrkA signaling is enhanced by exogenous GM1 ganglioside and this phenomenon is regarded as one of the functional aspects of GM1. The IgGs purified from patients' sera inhibited the NGF-TrkA signaling in GM1 pre-incubated PC12 cells. The degrees of inhibition by IgGs from patients paralleled their immunological reactivity to GM1. In addition, the IgGs also inhibited the neurite outgrowth of NGF-treated PC12 cells. Immunoglobulins in the rabbit sera, which were immunized by GM1, also caused a similar suppressive phenomenon. These results suggested that the anti-GM1 antibody could play roles in pathophysiology in anti-GM1 antibody positive GBS through interfering with the neurotrophic action of NGF and GM1 mediated signal modulation including NGF-TrkA signaling. It is suggested that the modulation of GM1 function is one important action of antibodies and could be one of the important mechanisms in GBS.

Topics: Adult; Animals; Autoantibodies; Female; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Male; Middle Aged; Nerve Growth Factor; PC12 Cells; Phosphorylation; Rats; Receptor, trkA; Signal Transduction

Guillain-Barré Syndrome (GBS) is a prototype of post-infectious autoimmune disease. A 76-year-old woman was treated for a renal abscess and developed muscle weakness in all four extremities, 18 days after the onset of infection. She was diagnosed with GBS on the basis of acute flaccid paralysis, hyporeflexia, nerve conduction studies (reduced amplitude of compound muscle action potentials), and high titers of IgG antibodies to GM1 and GalNAc-GD1a. GBS rarely occurs after sepsis and this case represents the first report of rapidly progressive GBS following Escherichia coli urosepsis.

Topics: Abscess; Aged; Autoantibodies; Disease Progression; Escherichia coli Infections; Female; G(M1) Ganglioside; Gangliosides; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Immunosorbent Techniques; Immunotherapy; Kidney Diseases; Neural Conduction; Paraplegia; Reflex, Abnormal; Time Factors

We identified IgG antibody to GM1 ganglioside in patients with axonal Guillain-Barré syndrome subsequent to Campylobacter jejuni enteritis, and that there is molecular mimicry between GM 1 and the bacterial lipooligosaccharide. On sensitization with GM1 as well as C. jejuni lipo-oligosaccharide, rabbits developed anti-GM1 IgG antibody and flaccid limb weakness. Paralyzed rabbits had pathological changes in their peripheral nerves identical to those present in axonal Guillain-Barré syndrome. These findings show that molecular mimicry is an important cause of Guillain-Barr6 syndrome. This new concept that carbohydrate mimicry can cause an autoimmune disease provides a clue to the resolution of the pathogenesis of other immune-mediated diseases.

Topics: Animals; Autoantibodies; Campylobacter Infections; Campylobacter jejuni; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Lipopolysaccharides; Molecular Mimicry; Rabbits

Guillain-Barré syndrome (GBS) is an acute, immune-mediated flaccid paralysis frequently associated with Campylobacter infection. Of two predominant GBS subtypes, a demyelinating subtype (acute inflammatory demyelinative polyneuropathy [AIDP]) predominates in the United States and Europe, and axonal subtype (acute motor axonal neuropathy [AMAN]) is the predominant form in China. Previous clinical studies suggested that AMAN also occurs in Mexican children. The purpose of this study was to describe the subtypes of GBS in children from Mexico City.. We prospectively studied 121 children admitted to two pediatric hospitals in Mexico City from 1996 to 2002. Clinical histories were obtained, electrophysiologic studies were performed to determine GBS subtype, and microbiologic studies were performed.. Of the 121 children, 46 had AMAN and 32 had AIDP. The male to female ratio was 1.3 for AMAN cases (mean age = 6.3) and 3.0 for AIDP cases (mean age = 7.0). There was a strong seasonal distribution of AMAN cases in July to September. Children with AMAN, but not AIDP, had worsening of illness during hospitalization as judged by peak severity scores. Vomiting was more likely in AIDP (28.1%) vs AMAN (6.5%) (p = 0.012) and diarrhea was more common in AMAN (32.6%) than AIDP (12.5%) (p = 0.06). IgG anti-GM1 antibody titers were higher in patients with AMAN vs AIDP (p = 0.067). Anti-GD1a antibodies were equally present in both groups. Anti GQ1b titers were higher in AMAN vs AIDP (p = 0.009). Campylobacter antibody responses were positive in 44.1% of patients with AMAN and 37.0% of patients with AIDP. Twenty patients (14 = AMAN, 6 = AIDP) had positive stool cultures for C jejuni. Two serotypes, HS:19 and HS:41, accounted for 6 of 10 Campylobacter isolates available for serotyping from these cases.. This study confirms that acute motor axonal neuropathy is an important Guillain-Barré syndrome subtype in Mexican children, is associated with diarrhea, and occurs seasonally.

Topics: Adolescent; Campylobacter Infections; Child; Child, Preschool; Diarrhea; Female; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Infant; Male; Mexico; Motor Neurons; Seasons

Topics: Antineoplastic Agents; Autoantibodies; Biomarkers; Biopsy; Carcinoma; Cystectomy; G(M1) Ganglioside; Guillain-Barre Syndrome; Hematuria; Humans; Male; Middle Aged; Neural Conduction; Paraneoplastic Syndromes, Nervous System; Peripheral Nerves; Recurrence; Treatment Outcome; Urinary Bladder Neoplasms

The expression of ganglioside-mimicking structures of Campylobacter jejuni lipooligosaccharides (LOS) is considered essential for the induction of antiganglioside antibodies that lead to Guillain-Barré syndrome (GBS). The galE gene in C. jejuni is involved in the biosynthesis of the LOS outer-core oligosaccharide structures. We have demonstrated that the C. jejuni HB9313 (HS:19) parental strain expresses a LOS structure containing GM1-like epitopes, and the C. jejuni knockout mutant of the galE gene expresses a truncated LOS structure without GM1-like epitopes. To clarify whether the ganglioside-like structures in Campylobacteri LOS are crucial for induction of antiganglioside antibody responses and neuropathy, we performed immunization experiments in guinea pig models using the parental strain HB9313 and its galE mutant derivative. The anti-GM1 IgG antibody responses in immunized animals were measured by enzyme-linked immunosorbent assay. Sciatic nerve specimens were evaluated pathologically. High levels of the anti-GM1 IgG antibody were induced in guinea pigs immunized with HB9313, but not in those immunized with the galE mutant. The mean percentage of abnormality of sciatic-nerve teased fibers from animals sensitized with C. jejuni HB9313 was significantly higher than from animals immunized with the galE mutant. Furthermore, significant changes were found in semithin sections of the sciatic nerve from animals inoculated with C. jejuni HB9313. The major pathological finding was axonal degeneration; no significant morphological findings, except for occasional demyelination, were observed in animals immunized with the galE mutant. These results indicate that ganglioside-mimicry structures in C. jejuni LOS are necessary for induction of antiganglioside antibody response and neuropathy.

Topics: Animals; Autoantibodies; Bacterial Proteins; Blotting, Western; Campylobacter jejuni; Electrophoresis, Polyacrylamide Gel; Epitopes; Female; G(M1) Ganglioside; Gene Expression Regulation, Bacterial; Gene Expression Regulation, Enzymologic; Guillain-Barre Syndrome; Guinea Pigs; Immunoglobulin G; Lipopolysaccharides; Molecular Mimicry; Nerve Degeneration; Nerve Fibers, Myelinated; Sciatic Nerve; UDPglucose 4-Epimerase

Anti-GM1 antibodies of the IgG isotype are found in serum from patients with Guillain-Barré syndrome. In normal human sera, anti-GM1 IgM-antibodies are commonly present, but their IgG counterpart has not been previously demonstrated. During routine screening, we found a normal human serum with a high titer of anti-GM1 IgG-antibodies (IgG1 subclass). Affinity estimation by soluble antigen-binding inhibition indicated that they are low-affinity antibodies with IC50 values between one and two orders of magnitude higher than those of anti-GM1 IgG-antibodies from Guillain-Barré patients. Various antibody parameters remained fairly constant for 1 year, in additional serum samples taken at 4-month intervals. Such anti-GM1 IgG1-antibodies were not detected in > 100 other normal serum samples tested, indicating a very low frequency in the general population. The low affinity of these unusually present antibodies could explain the absence of disease, despite their relatively high titer. The significance of this finding in the origin of disease-associated anti-GM1 antibodies is discussed.

Topics: Adult; Antibody Affinity; Autoantibodies; Chromatography, High Pressure Liquid; Enzyme-Linked Immunosorbent Assay; Female; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Immunoglobulin G

Guillain-Barre syndrome (GBS), a postinfectious autoimmune-mediated neuropathy, is a serious complication after Campylobacter jejuni enteritis.. To investigate the bacterial risk factors for developing GBS, genotypes, serotypes, and ganglioside mimics on lipo-oligosaccharide (LOS) were analyzed in C. jejuni strains from Japanese patients.. Strains from patients with GBS had LOS biosynthesis locus class A more frequently (72/106; 68%) than did strains from patients with enteritis (17/103; 17%). Class A strains predominantly were serotype HS:19 and had the cstII (Thr51) genotype; the latter is responsible for biosynthesis of GM1-like and GD1a-like LOSs. Both anti-GM1 and anti-GD1a monoclonal antibodies regularly bound to class A LOSs, whereas no or either antibody bound to other LOS locus classes. Mass-spectrometric analysis showed that a class A strain carried GD1a-like LOS as well as GM1-like LOS. Logistic regression analysis showed that serotype HS:19 and the class A locus were predictive of the development of GBS.. The high frequency of the class A locus in GBS-associated strains, which was recently reported in Europe, provides the first GBS-related C. jejuni characteristic that is common to strains from Asia and Europe. The class A locus and serotype HS:19 seem to be linked to cstII polymorphism, resulting in promotion of both GM1-like and GD1a-like structure synthesis on LOS and, consequently, an increase in the risk of producing antiganglioside autoantibodies and developing GBS.

Topics: Antibodies, Bacterial; Campylobacter Infections; Campylobacter jejuni; Enteritis; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Lipopolysaccharides; Risk Factors

Human ganglioside-like structures, such as GM1, found on some Campylobacter jejuni strains have been linked to inducing the Guillain-Barré Syndrome (GBS). This study shows that a C. jejuni strain without GM1-like molecules acquired large DNA fragments, including lipooligosaccharide synthesis genes, from a strain expressing GM1-like molecules and consequently transformed into a number of potential GBS-inducible transformants, which exhibited a high degree of genetic and phenotypic diversity.

Topics: Bacterial Proteins; Campylobacter jejuni; DNA, Bacterial; Electrophoresis, Gel, Pulsed-Field; G(M1) Ganglioside; Gene Transfer, Horizontal; Guillain-Barre Syndrome; Humans; Lipopolysaccharides; Molecular Mimicry; Multigene Family; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Recombination, Genetic; Transformation, Bacterial

New Zealand white rabbits were immunized with a lipopolysaccharide (LPS) extracted from a Campylobacter jejuni HS:19 strain isolated from a GBS patient expressing GM1 and GD1a-like epitopes, Freund's adjuvant (group I) and Freund's adjuvant plus keyhole lympet hemocyanin (KLH) (group II). Both groups showed high titers of anti-LPS and anti-GM1 and lower titers of anti-GD1b and anti-GD1a antibodies. Weakness and axonal degeneration in sciatic nerves was detected in 1/11 of group I and 6/7 of group II. This model replicates, at least in part, the pathogenetic process hypothesized in the human axonal GBS with antiganglioside antibodies post C. jejuni infection and indicates that KLH plays an additional role in neuropathy induction.

Topics: Animals; Antibodies, Bacterial; Blotting, Western; Campylobacter jejuni; Disease Models, Animal; Electrophoresis, Polyacrylamide Gel; Enzyme-Linked Immunosorbent Assay; Epitopes; G(M1) Ganglioside; Gangliosides; Gene Expression; Guillain-Barre Syndrome; Humans; Immunization; Lipopolysaccharides; Male; Polyradiculoneuropathy; Rabbits; Time Factors

The authors reported the neurological disease spectrum associated with autoantibodies against minor gangliosides GM1b and GalNAc-GD1a. IgG and IgM antibody reactivity against gangliosides GM1, GM2, GM1b, GD1a, GalNAc-GD1a and GQ1b was investigated in sera from 7000 consecutive patients who had various neurological conditions. The clinical diagnoses for 456 anti-GM1b-positive patients were Guillain-Barré syndrome (GBS, 71%), atypical GBS with preserved deep tendon reflexes (12%), Fisher syndrome (10%), Bickerstaff's brainstem encephalitis (2%), ataxic GBS (2%) and acute ophthalmoparesis (1%). For 193 anti-GalNAc-GD1a-positive patients, the diagnoses were GBS (70%), atypical GBS (16%), Fisher syndrome (10%) and Bickerstaff's brainstem encephalitis (3%). Of the patients with GBS or atypical GBS, 28% of 381 anti-GM1b-positive and 31% of 166 anti-GalNAc-GD1a-positive patients had neither anti-GM1 nor anti-GD1a antibodies. Of those patients with Fisher syndrome, Bickerstaff's brainstem encephalitis, ataxic GBS or acute ophthalmoparesis, 33% of 67 anti-GM1b-positive, and 52% of 25 anti-GalNAc-GD1a-positive patients had no anti-GQ1b antibodies. Autoantibodies against GM1b and GalNAc-GD1a are associated with GBS, Fisher syndrome and related conditions. These antibodies should provide useful serological markers for identifying patients who have atypical GBS with preserved deep tendon reflexes, ataxic GBS, Bickerstaff's brainstem encephalitis or acute ophthalmoparesis, especially for those who have no antibodies to GM1, GD1a or GQ1b. A method to prepare GM1b was developed.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Autoantibodies; Autoimmune Diseases of the Nervous System; Biomarkers; Child; Child, Preschool; Encephalomyelitis, Acute Disseminated; Female; G(M1) Ganglioside; Gangliosides; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Immunoglobulin M; Male; Middle Aged; Miller Fisher Syndrome; Nervous System; Predictive Value of Tests; Retrospective Studies

We developed testing kits for anti-GM1 and anti-GQ1b IgG antibodies and examined their utilities in supporting the diagnosis of Guillain-Barré syndrome (GBS) and Fisher syndrome (FS). Anti-GM1 antibody was detected in 49% of 95 patients with GBS and in 5% or less of disease and normal controls. Anti-GQ1b antibody was detected in 85% of 55 patients with FS, whereas in none of the controls. Eight GBS patients, in whom anti-GM1 IgG antibody was judged negative using the kit, were found to have other anti-ganglioside IgG antibodies. Four of them showed ophthalmoplegia and had anti-GQ1b IgG antibody. Detection of anti-GM1 IgG antibody in GBS and of anti-GQ1b IgG antibody in FS within one week after the disease onset were significantly more frequent compared to albuminocytologic dissociation in the cerebrospinal fluids (GBS, 58% vs 32%; FS, 89% vs 20%). These findings indicate that our testing kits are useful for supporting the early diagnosis of GBS and FS.

Topics: Adult; Autoantibodies; Female; G(M1) Ganglioside; Gangliosides; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Male; Middle Aged; Miller Fisher Syndrome; Reagent Kits, Diagnostic

High antibody affinity has been proposed as a disease determinant factor in neuropathies associated with anti-GM1 antibodies. An experimental model of Guillain-Barré syndrome, induced by immunization of rabbits with bovine brain gangliosides or GM1, was described recently (Yuki et al. [2001] Ann. Neurol. 49:712-720). We searched plasma from these rabbits, taken at disease onset and 1 or 2 weeks prior to onset, for the presence of high-affinity anti-GM1 IgG antibodies. Affinity was estimated by soluble antigen binding inhibition. High-affinity antibodies (binding inhibition by 10(-9) M GM1) were detected at disease onset but not before. No such difference was found for other antibody parameters such as titer, fine specificity, and population distribution. These findings support the proposed role of high affinity as an important factor in disease induction by anti-GM1 antibodies.

Topics: Animals; Antibody Affinity; Antibody Specificity; Autoantibodies; Binding Sites, Antibody; Cattle; Chromatography, Thin Layer; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; G(M1) Ganglioside; Guillain-Barre Syndrome; Rabbits; Time Factors

Guillain-Barré syndrome (GBS) is a heterogeneous disorder according to clinical, electrophysiological, immunologic and pathologic findings. It has usually been considered as an immune-mediated polyneuropathy clinically characterised by acute symmetric muscle weakness and areflexia. We describe a patient who, after a Campylobacter jejuni infection, developed an acute motor-sensory neuropathy with marked and persistent asymmetry of clinical and electrophysiological findings. He had a high titre of anti-GM1 IgG antibodies and cytoalbuminologic dissociation and was responsive to intravenous immunoglobulins. Investigations and three years of follow-up excluded mimics of GBS. Tendon areflexia has recently been challenged as a mandatory diagnostic criterion in GBS; likewise marked and persistent motor asymmetry does not exclude the diagnosis of GBS.

Topics: Adolescent; Autoantibodies; Campylobacter Infections; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Male; Neural Conduction; Reaction Time

Serum antibody activities to mixtures of a ganglioside and various phospholipids were compared with those to a ganglioside alone in 30 anti-GM1 IgG-positive GBS patients and 30 anti-GQ1b IgG-positive Miller Fisher syndrome (MFS) patients. Anti-GM1-positive sera had higher antibody reactivities against a mixture of GM1 and several phospholipids including PA, PI and PS, than against GM1 alone. In contrast, in case of anti-GQ1b antibody, no phospholipid provided significant enhancement. Sphingomyelin provided decrease of the activity for both anti-GM1 and anti-GQ1b IgG. The effects of phospholipids must be considered to determine the pathogenetic role of antiganglioside antibodies in GBS and MFS.

Topics: Adjuvants, Immunologic; Binding Sites, Antibody; Cardiolipins; G(M1) Ganglioside; Gangliosides; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Immunoglobulin M; Lysophosphatidylcholines; Lysophospholipids; Phosphatidic Acids; Phosphatidylcholines; Phosphatidylinositols; Phosphatidylserines; Phospholipids; Sphingomyelins

In Guillain-Barré syndrome (GBS), anti-ganglioside antibodies are strongly associated with the acute motor axonal neuropathy (AMAN) form, but there are also cases of the demyelinating form of GBS (acute inflammatory demyelinating polyneuropathy [AIDP]) with anti-ganglioside antibodies.. To elucidate the patterns and sequential changes in electrodiagnostic abnormalities of anti-ganglioside-positive GBS.. Detailed serial electrodiagnostic findings were reviewed for 51 patients with GBS. Anti-ganglioside antibodies were measured by ELISA.. Antibodies to GM1, GM1b, GD1a, or GalNAc-GD1a were present in 25 patients. Of these, 12 (48%) showed the AMAN pattern, 5 (20%) the AIDP pattern, and 3 (12%) isolated F-wave absence in the first examination. All five patients with the AIDP pattern showed prolonged distal latencies, but three eventually showed the AMAN pattern or rapid normalization. The remaining two still had similarly prolonged distal latencies in weeks 4 to 6, but the serial changes were distinct from those in the anti-ganglioside-negative AIDP patients who showed progressive increases in distal latencies over 2 months after onset.. Besides the simple axonal degeneration pattern, patients with anti-ganglioside-positive Guillain-Barre syndrome can show transient conduction slowing/block in the distal or proximal nerve segments, mimicking demyelination, but anti-ganglioside antibodies do not appear to be associated with acute inflammatory demyelinating polyneuropathy.

Topics: Adult; Autoantibodies; Axons; Disease Progression; Electrodiagnosis; Female; G(M1) Ganglioside; Gangliosides; Guillain-Barre Syndrome; Humans; Male; Middle Aged; Neural Conduction; Peripheral Nerves; Predictive Value of Tests

A comparative study on the role of Campylobacter jejuni (CJ) HB9313 and galE mutant in inducing experimental sciatic nerve damage was conducted in guinea pigs in order to explore whether CJ lipo-oligosaccharide (LOS) is critical component associated with peripheral nerve lesions and find experimental evidence for the presumption of molecular mimicry on the pathogenesis of Guillain-Barre syndromes (GBS) with CJ antecedent infection.. A total of 32 guinea pigs were randomly divided into four groups: parental strain group (n = 10), galE mutant group (n = 10), control group (n = 6) and PBS group (n = 6), and immunized with the whole cell antigens of CJ HB9313 with Freund's adjuvant (FA), the whole cell antigens of galE mutant (without ganglioside-like structure) with FA, PBS with FA, and PBS alone, respectively. Enzyme-linked immunosorbent assay (ELISA) was employed to detect anti-LOS and anti-ganglioside GM1 antibodies in sera of these animals, and comparative morphologic studies of pathologic changes were carried out on the sciatic nerves, including examination of teasing fibers, examination of semithin sections made from epon-embedded tissue blocks under light microscope and transmission electron microscope.. ELISA results indicated that after immunization, the levels of anti-LOS IgG antibody were significantly elevated in animals from parental strain group and galE mutant group as compared with those before immunization (P < 0.01). No statistically significant difference was found between the two groups. However, the mean optical densities (ODs) of IgG antibody against GM1 at 14 and 28 day after immunization, in parental strain group, were 0.661 +/- 0.290 and 0.984 +/- 0.025, respectively, significantly higher than those of galE mutant group, which were 0.193 +/- 0.078 and 0.180 +/- 0.063 (P < 0.01). The results of morphologic examination on sciatic nerves showed that for teased-fiber study, incidence of pathologic abnormalities of teased fibers from animals of galE mutant group was 4.9% (98/2000), significantly lower than that from parental strain group, which was 16% (320/2000), characterized by predominantly axonal degeneration. The difference between them was highly significant statistically (P < 0.01). Examination of semithin sections of sciatic nerves also revealed that obvious pathological changes occurred in the animals from parental strain group, while only minimal abnormalities could be seen from galE mutant group, there was a significant differences between them (P < 0.01). In parental strains group, the predominant pathologicanl change was axonal degeneration with considerable variation in severity. These morphologic changes were confirmed by electron microscopy.. Compared with parental strain, galE mutant without ganglioside-like structure no longer could induce anti-GM1 antibodies, nor induce obvious immune damage of peripheral nerves in experimental guinea pigs. The results of this study provide a strong support to the hypothesis of molecular mimicry as a pathogenesis in patients with GBS following CJ antecedent infection.

Topics: Animals; Antibodies, Bacterial; Campylobacter jejuni; G(M1) Ganglioside; Guillain-Barre Syndrome; Guinea Pigs; Immunization; Lipopolysaccharides; UDPglucose 4-Epimerase

This study was performed to determine whether increased ganglioside-specific T cell reactivity can be detected in the peripheral blood of patients with Guillain-Barre syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). T cell responsiveness to the gangliosides GM1, GM3, GD1a, GD1b, GD3, GT1b, GQ1b and sulphatide was assessed in peripheral blood mononuclear cells from untreated GBS patients (57), CIDP patients (43), patients with other peripheral neuropathies (55) and healthy control subjects (74) in a standard 6-day proliferation assay. Increased T cell reactivity to GM1 occurred in GBS patients compared to healthy controls and patients with other neuropathies. There was increased reactivity to GM3 in GBS patients compared to patients with other neuropathies but not compared to healthy controls. The frequencies of increased T cell reactivity to GM1 and GM3 in CIDP patients were intermediate between those of GBS patients and controls. We suggest that T cell reactivity to gangliosides might play a contributory role in the pathogenesis of GBS and perhaps CIDP.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cell Proliferation; Chi-Square Distribution; Female; G(M1) Ganglioside; Gangliosides; Guillain-Barre Syndrome; Humans; Male; Middle Aged; Odds Ratio; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; T-Lymphocytes; Tetanus Toxoid

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired disorder of the peripheral nervous system with a probable auto-immune pathogenesis. The nature of the responsible autoantigens is unclear in most patients. We used the Western immunoblot technique to seek antibodies to peripheral nerve protein antigens. Sera from eight of 32 (25%) CIDP patients, 12 of 37 (32%) Guillain-Barré syndrome (GBS) patients, zero of 30 (0%) chronic idiopathic axonal polyneuropathy patients and two of 39 (5%) healthy control subjects contained anti-peripheral nerve protein antibodies. The frequency of such antibodies was significantly greater in both CIDP (p = 0.04) and GBS (p = 0.003) patients than in normal control subjects. For CIDP patients, there were non-significant trends for antibodies to be more common in females and in those who responded to treatment with either intravenous immunoglobulin or plasma exchange. The commonest antibodies were directed against a band at 28 kDa, resembling that labelled by a monoclonal antibody against myelin protein zero (P0). Six CIDP and seven GBS patients' sera reacted with this band. These results support the view that antibodies to myelin proteins, and especially P0, are present in the serum of some patients with CIDP and GBS.

Topics: Adult; Aged; Antibodies; Blotting, Western; Enzyme-Linked Immunosorbent Assay; Female; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Male; Middle Aged; Molecular Weight; Myelin Proteins; Peripheral Nerves; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; Time Factors

Molecular mimicry of gangliosides by Campylobacter jejuni lipooligosaccharides (LOSs) in the induction of anti-ganglioside antibodies has been hypothesised to contribute to GBS development. Rabbits were immunised with ganglioside-mimicking C. jejuni LOSs and anti-LOS responses were analysed using passive haemagglutination, and anti-ganglioside responses by enzyme-linked immunosorbent assay and thin-layer chromatography with immunostaining. High titres of anti-LOS antibodies were demonstrated in rabbit antisera that were cross-reactive with a panel of gangliosides. Non-ganglioside-mimicking C. jejuni HS:3 LOS induced a strong anti-LOS response, but no anti-ganglioside antibodies. Control rabbit antisera had no anti-LOS or -ganglioside responses. Moreover, IgG from a patient treated with parenteral gangliosides, who exhibited Guillain-Barré syndrome, had antibodies reactive with C. jejuni LOS. Biotinylated IgG fractions from the rabbit and the patient sera recognised epitopes at the nodes of Ranvier in sectioned human nerves, whereas fractions from controls did not. This study demonstrates that immunisation with ganglioside-mimicking C. jejuni LOS triggers the production of cross-reactive anti-ganglioside antibodies that recognise epitopes at the nodes of Ranvier.

Topics: Animals; Antibodies, Bacterial; Binding Sites, Antibody; Campylobacter jejuni; Cross Reactions; Epitopes; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Immunohistochemistry; Lipopolysaccharides; Molecular Mimicry; Rabbits; Ranvier's Nodes

Brucella melitensis is a facultative intracellular bacterium that can survive inside macrophages and the causative agent of brucellosis. In the present study, we found that a lipooligosaccharide of B. melitensis has a GM1 ganglioside-like structure and shows a strong antibody response in mice. The cholera toxin B subunit, which binds to GM1 ganglioside specifically, reacted with the surface of B. melitensis. Immunization with B. melitensis induced the production of anti-GM1 ganglioside antibodies in mice and serum from immunized mice showed a cross-reaction with Guillain-Barré syndrome (GBS)-associated Campylobacter jejuni, but not non-GBS-associated C. jejuni. When B. melitensis was treated with a neuraminidase, antibody responses disappeared. B. melitensis immunization induced the production of anti-GM1 ganglioside antibodies in BALB/c mice but not in C57BL/6 and ddY mice, and for BALB/c mice, immunization with B. melitensis induced much greater production of anti-GM1 ganglioside than GBS-associated C. jejuni. Flaccid limb weakness was observed in B. melitensis immunized mice. These results suggest that B. melitensis is a new etiological agent for GBS and that immunological responses between it and GBS-associated C. jejuni in the mouse model may be different.

Topics: Animals; Antibodies, Bacterial; Brucella melitensis; Brucellosis; Campylobacter jejuni; Cholera Toxin; Cross Reactions; Disease Models, Animal; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Immunization; In Vitro Techniques; Lipopolysaccharides; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Molecular Mimicry

The Inflammatory Neuropathy and Treatment (INCAT) group developed a standardized ELISA method for the detection of serum anti-GM1 antibodies. The diagnostic value of anti-GM1 antibodies determined by this method has not yet been established in large groups of patients. We assessed the reproducibility, sources of variation, optimal cut-off values and evaluated the diagnostic relevance of the INCAT-ELISA in various groups of patients and controls (N=1232). The coefficient of variance was 11.2% for IgM and 3.8% for IgG. High IgG titers were only found in Guillain-Barré syndrome (GBS) and other inflammatory polyneuropathies. High IgM titers were associated with GBS and multifocal motor neuropathy. Low IgM titers had no additional diagnostic value. The INCAT-ELISA is a reliable test with additional diagnostic value in specific clinical situations.

Topics: Autoantibodies; Enzyme-Linked Immunosorbent Assay; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Immunoglobulin M; Peripheral Nerves; Predictive Value of Tests; Reproducibility of Results

Ganglioside epitopes on Campylobacter jejuni are hypothesized as the key to the development and characterization of Guillain-Barré syndrome (GBS), but a comprehensive theory has yet to be established. A C jejuni gene, cst-II, involved in the biosynthesis of ganglioside-like lipo-oligosaccharide, shows a polymorphism (Asn/Thr51) that affects ganglioside epitopes.. To examine the hypothesis that this polymorphism determines autoantibody reactivity, and thereby neurologic presentations in GBS.. C jejuni isolates were collected from 105 GBS (including its variants) and 65 uncomplicated enteritis patients. The authors examined the frequency of cst-II and polymorphism (Asn/Thr51) in connection with the bacterial ganglioside epitopes, autoantibody reactivities against GM1, GD1a, and GQ1b, and patients' neurologic findings.. Neuropathic strains more frequently had cst-II, in particular cst-II (Thr51), than did enteritic ones (85% vs 52%; p < 0.001). Strains with cst-II (Asn51) regularly expressed the GQ1b epitope (83%), whereas those with cst-II (Thr51) had the GM1 (92%) and GD1a (91%) epitopes. The presence of these bacterial epitopes in neuropathy patients corresponded to autoantibody reactivity. Patients infected with C jejuni (Asn51) more often were positive for anti-GQ1b IgG (56% vs 8%; p < 0.001) and had ophthalmoparesis (64% vs 13%; p < 0.001) and ataxia (42% vs 11%; p = 0.001). Patients who had C jejuni (Thr51) more frequently were positive for anti-GM1 (88% vs 35%; p < 0.001) and anti-GD1a IgG (52% vs 24%; p = 0.006) and had limb weakness (98% vs 71%; p < 0.001).. The genetic polymorphism of C jejuni determines autoantibody reactivity as well as the clinical presentation of Guillain-Barré syndrome (GBS), possibly through modification of the host-mimicking molecule. The GBS paradigm is the first to explain the detailed pathogenesis of a postinfectious, autoimmune-mediated, molecular mimicry-triggering disorder.

Topics: Autoantibodies; Campylobacter Infections; Campylobacter jejuni; Epitopes; G(M1) Ganglioside; Gangliosides; Gene Expression Regulation, Bacterial; Guillain-Barre Syndrome; Humans; Lipopolysaccharides; Molecular Mimicry; Mutation; Polymorphism, Genetic; Species Specificity

Ataxic Guillain-Barré syndrome (GBS) associated with anti-GQ1b IgG antibody has been reported. We, however, have had a patient with ataxic GBS who had IgG antibodies to the minor gangliosides GM1b and GalNAc-GD1a, and we therefore retrospectively investigated the clinical features of patients who had antibodies to GM1b or GalNAc-GD1a, but not to GQ1b. Information on patients' antecedent illnesses, initial symptoms, neurological signs, and CSF findings was reviewed in those with ataxic GBS or Fisher syndrome (FS) with anti-GM1b or anti-GalNAc-GD1a IgG antibodies. We tested whether the anti-GM1b and anti-GalNAc-GD1a antibodies are cross-reactive and constructed three-dimensional structural models of GM1b and GalNAc-GD1a. Ataxic GBS was diagnosed in 1 of 65 patients who had both anti-GM1b and anti-GalNAc-GD1a antibodies and in 3 of 159 patients who had anti-GM1b antibody without anti-GalNAc-GD1a antibody: FS was diagnosed in 1 of the 159 patients and in 1 of 35 who had anti-GalNAc-GD1a antibody without anti-GM1b antibody. All the patients' antibodies to GM1b or GalNAc-GD1a were associated with the IgG isotype. The clinical features of patients with ataxic GBS associated with anti-GM1b or anti-GalNAc-GD1a IgG antibodies did not differ from those of patients who had anti-GQ1b IgG antibody. Absorption study findings for serum from the patient who had both anti-GM1b and anti-GalNAc-GD1a IgG antibodies showed significant absorbance of anti-GM1b IgG antibody by GalNAc-GD1a and of anti-GalNAc-GD1a IgG antibody by GM1b, indicating that these antibodies are cross-reactive. This is the first report of ataxic GBS or FS associated with anti-GM1b or anti-GalNAc-GD1a IgG antibodies. These autoantibodies, as well as anti-GQ1b IgG antibody, may function in the development of some patients with ataxic GBS and FS.

Topics: Adult; Aged; Aged, 80 and over; Antibody Specificity; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Female; G(M1) Ganglioside; Gangliosides; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Male; Middle Aged; Retrospective Studies

Patients with Guillain-Barré syndrome (GBS) after Mycoplasma pneumoniae infection often have antibodies to galactocerebroside (GalC). Electrodiagnosis may show acute inflammatory demyelinating polyneuropathy (AIDP).. The authors report a patient with acute motor axonal neuropathy (AMAN) after Mycoplasma infection and review seven cases of Mycoplasma-associated GBS. They investigated anti-GalC serology under various conditions associated with Mycoplasma infection.. The patient had immunoglobulin (Ig)G and IgM antibodies against GM1 and GalC, which cross-reacted. During the acute phase, IgM selectively immunostained axons. The cholera toxin B-subunit and rabbit anti-GM1 IgG stained a band in the lipid extract from M pneumoniae, indicative of the presence of a GM1 epitope. Six Mycoplasma-associated GBS patients with anti-GalC antibodies had non-AIDP electrodiagnoses, whereas one with Mycoplasma-associated AIDP had no anti-GalC antibodies. Anti-GalC antibodies were positive in two of five patients who had neurologic diseases other than GBS after Mycoplasma infection and in one of 12 who had acute respiratory disease caused by M pneumoniae not followed by a neurologic disease.. Anti-GalC antibodies in Mycoplasma-associated GBS may be an epiphenomenon. In certain cases, anti-GM1 antibodies induced by molecular mimicry with M pneumoniae may cause acute motor axonal neuropathy.

Topics: Acute Disease; Adult; Animals; Autoantibodies; Axons; Cross Reactions; Electrodiagnosis; Enzyme-Linked Immunosorbent Assay; Epitopes; G(M1) Ganglioside; Galactosylceramides; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Immunoglobulin M; Immunoglobulins, Intravenous; Male; Molecular Mimicry; Mycoplasma Infections; Neural Conduction; Rabbits; Rats; Serologic Tests

Topics: Autoantibodies; Drug Therapy, Combination; G(M1) Ganglioside; Glucocorticoids; Guillain-Barre Syndrome; Humans; Immunoglobulins, Intravenous; Methylprednisolone

Molecular mimicry between microbial and self-components is postulated as the mechanism that accounts for the antigen and tissue specificity of immune responses in postinfectious autoimmune diseases. Little direct evidence exists, and research in this area has focused principally on T cell-mediated, antipeptide responses, rather than on humoral responses to carbohydrate structures. Guillain-Barré syndrome, the most frequent cause of acute neuromuscular paralysis, occurs 1-2 wk after various infections, in particular, Campylobacter jejuni enteritis. Carbohydrate mimicry [Galbeta1-3GalNAcbeta1-4(NeuAcalpha2-3)Galbeta1-] between the bacterial lipooligosaccharide and human GM1 ganglioside is seen as having relevance to the pathogenesis of Guillain-Barré syndrome, and conclusive evidence is reported here. On sensitization with C. jejuni lipooligosaccharide, rabbits developed anti-GM1 IgG antibody and flaccid limb weakness. Paralyzed rabbits had pathological changes in their peripheral nerves identical with those present in Guillain-Barré syndrome. Immunization of mice with the lipooligosaccharide generated a mAb that reacted with GM1 and bound to human peripheral nerves. The mAb and anti-GM1 IgG from patients with Guillain-Barré syndrome did not induce paralysis but blocked muscle action potentials in a muscle-spinal cord coculture, indicating that anti-GM1 antibody can cause muscle weakness. These findings show that carbohydrate mimicry is an important cause of autoimmune neuropathy.

Topics: Animals; Antibodies, Monoclonal; Autoantibodies; Campylobacter jejuni; Cells, Cultured; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Immunization, Passive; Immunoglobulin G; Lipopolysaccharides; Male; Molecular Mimicry; Muscle Fibers, Skeletal; Paralysis; Rabbits; Spinal Cord; Spinal Nerve Roots

In Guillain-Barré syndrome (GBS), the destruction or malfunction of blood-nerve barrier (BNB) has been considered to be the beginning of the disease process. It is unclear whether sera from patients with GBS can open the BNB, and which component of patient sera is most important in the dysregulation of the BNB.. The authors evaluated the effect of sera from patients with GBS on permeability of an in vitro BNB model using bovine endoneurial microvascular endothelial cells (PnMEC) cultured on the luminal side of a collagen-coated culture insert (pore size: 0.4 micro m).. PnMEC monolayers challenged by GBS sera showed significantly lower transendothelial electrical resistance and higher clearance of [carboxyl-(14)C]-inulin with or without complement. Sera with anti-GM1 antibody showed greater loosening of the barrier than others. This effect decreased significantly after incubation with pure GM1 antigen, suggesting the importance of anti-GM1 antibody in BNB dysregulation. Serial analyses of [carboxyl-(14)C]-inulin clearance in four patients disclosed a favorable effect of plasmapheresis in restoring BNB function in some cases.. The authors found an unfavorable effect of sera from patients with GBS on BNB function, supporting involvement of humoral factors causing BNB derangement in the acute stage. Serial evaluation of permeability change using the authors' in vitro system might be useful for the clinical assessment of BNB derangement in individual patients.

Topics: Adult; Animals; Autoantibodies; Blood Proteins; Capillary Permeability; Cattle; Cauda Equina; Cells, Cultured; Complement System Proteins; Electric Impedance; Endothelium, Vascular; Female; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Inulin; Male; Middle Aged; Models, Biological; Plasma Exchange; Plasmapheresis; Predictive Value of Tests

Topics: Adult; Autoantibodies; Brain Stem; Encephalitis; Female; G(M1) Ganglioside; Gangliosides; Guillain-Barre Syndrome; Humans; Miller Fisher Syndrome; Muscle Weakness; Ophthalmoplegia

Anti-GM1 immunoglobulin G (IgG) antibodies are frequently present in sera from patients with Guillain-Barré syndrome (GBS). A previous report on a patient who had a neuropathy with immunoglobulin M (IgM) M-protein binding to a conformational epitope formed by phosphatidic acid (PA) and gangliosides prompted us to investigate the binding of IgG antibodies in GBS sera to a mixture of GM1 and PA (GM1/PA). Of 121 GBS patients, 32 had anti-GM1 IgG antibodies. All 32 also had antibody activity against GM1/PA. Twenty-five (78%) of 32 patients had greater activity against GM1/PA than against GM1 alone. Twelve patients who had no anti-GM1 IgG antibodies had IgG antibody activity against GM1/PA. No GBS patient had IgG antibody against PA alone. In contrast, two rabbit anti-GM1 antisera had greater activity against GM1 alone than against GM1/PA. IgG antibody with greater binding activity against a mixture of GM1 and a phospholipid than against GM1 alone may have an important role in the pathogenesis of GBS and has implications for diagnosis.

Topics: Acute Disease; Antibody Specificity; Autoantibodies; Biomarkers; Enzyme-Linked Immunosorbent Assay; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Phospholipids

Anti-GM1 and anti-GM1b antibodies are frequently present in patients with Guillain-Barré syndrome (GBS) and accordingly, the two antibodies often coexist in the same patient. In order to study clinical and laboratory features of anti-GM1b-positive GBS, we analyzed the data of patients with anti-GM1b IgG antibody but no anti-GM1 IgG antibody. Of 86 consecutive patients, 10 had anti-GM1b antibody alone and frequently had acute motor axonal neuropathy (AMAN, 80%) and Campylobacter jejuni infection (60%). Of 10 patients with anti-GM1 antibody alone, four had AMAN, and two had C. jejuni infection. These results showed that GM1b could be a target molecule of autoantibody in the AMAN form of GBS subsequent to C. jejuni infection.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antibodies; Campylobacter Infections; Campylobacter jejuni; Child; Child, Preschool; Enzyme-Linked Immunosorbent Assay; Female; G(M1) Ganglioside; Gangliosidosis, GM1; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Male; Middle Aged

To determine whether the anti-GM1 antibody IgG subclass (IgG1 to 4) is associated with clinical profiles and patterns of recovery in Guillain-Barré syndrome (GBS).. The IgG subclassification of anti-GM1 antibody was examined and compared with clinical data on 42 GBS patients positive for the antibody.. Frequent anti-GM1 antibody subclasses were IgG1 (76%) and IgG3 (31%). IgG1 antibody was associated with preceding gastroenteritis and Campylobacter jejuni serology, whereas IgG3 antibody was associated with preceding respiratory infection. Although the severity at nadir was similar for IgG1- and IgG3-positive patients, the percentage of patients who could not walk independently was greater for the IgG1-positive group 1 month (42 vs 0%; p = 0.02), 3 months (28 vs 0%), and 6 months (25 vs 0%) after onset. Rapid recovery within 1 month occurred frequently in the patients with the IgG3 antibody but rarely in those with the IgG1 antibody (67 vs 11%; p = 0.003).. The IgG1 subclass of anti-GM1 antibody is a major subtype indicative of slow recovery, whereas isolated elevation of IgG3 subclass antibody titer suggests rapid recovery. Variation in subclass patterns may depend on which pathogen precipitates GBS.

Topics: Adult; Autoantibodies; Campylobacter Infections; Campylobacter jejuni; Convalescence; Female; G(M1) Ganglioside; Gastroenteritis; Guillain-Barre Syndrome; Haemophilus Infections; Haemophilus influenzae; Humans; Immunoglobulin G; Immunoglobulins, Intravenous; Male; Middle Aged; Plasmapheresis; Treatment Outcome

We report the first case of axonal Guillain-Barré syndrome (GBS) associated with axonal Charcot-Marie-Tooth disease (CMT). A 30-year-old Japanese man, who had suffered leg atrophy and foot deformity since childhood, developed acute weakness in his four limbs following an upper respiratory tract infection. Nerve conduction studies showed low compound muscle action potential (CMAP) and sensory nerve action potential (SNAP) amplitudes in all the nerves tested. Serial studies showed a rapid increase in CMAP amplitude, but no significant change in SNAP, which indicates that the acute event selectively involved motor axons and was superimposed on a baseline motor-sensory axonal neuropathy, probably CMT Type 2. Elevated serum IgG antibodies against GM1 and GM1b, an increase in CSF protein, and rapid clinical and electrophysiological recovery after plasma exchange support the diagnosis of a pure motor axonal form of GBS, acute motor axonal neuropathy. The association may be coincidental, but a particular susceptibility to axonal damage of CMT2 cannot be excluded.

Topics: Adult; Axons; Charcot-Marie-Tooth Disease; Electrophysiology; Evoked Potentials; G(M1) Ganglioside; Gangliosides; Guillain-Barre Syndrome; Humans; Male; Muscles; Neural Conduction; Peripheral Nerves; Reaction Time; Respiratory Tract Infections; Sural Nerve

We studied the relationship between post-polio syndrome (PPS) and GM1 antibodies, since such antibodies have been associated with PPS and motor neuron disorders. Sera from 144 patients with previous poliomyelitis (105 paralytic, 22 nonparalytic and 17 PPS), 60 with previous Guillain-Barré syndrome, 44 with amyotrophic lateral sclerosis (ALS) and 22 healthy blood donors were analyzed with ELISA for GM1 IgM, IgG and IgA antibodies. GM1 antibodies were present in 14% of the PPS patients, but the prevalence did not differ significantly from that of the other groups. Our study does not support the hypothesis that GM1 antibodies are involved in the pathogenesis of PPS.

Topics: Adult; Aged; Aged, 80 and over; Amyotrophic Lateral Sclerosis; Autoantibodies; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Immunoglobulin M; Male; Middle Aged; Motor Neurons; Peripheral Nerves; Poliomyelitis; Postpoliomyelitis Syndrome

Topics: Antibodies, Anti-Idiotypic; Biomarkers; Enzyme-Linked Immunosorbent Assay; Female; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Latex Fixation Tests; Male; Sensitivity and Specificity

Rapid detection of serum anti-ganglioside antibodies in Guillain-Barré syndrome (GBS) could facilitate early diagnosis and early initiation of treatment, which might shorten the term of illness and reduce sequelae. We examined serum anti-ganglioside antibodies in patients with GBS using the latex agglutination assay developed by Alaedini and Latov (J Immunoassay 21: 377-386, 2000) with some modifications.. We used 75 sera from GBS patients, which exhibited IgG anti-GM1, GD1b, or GQ1b, or IgM anti-GM2 antibodies on previous enzyme-linked immunosorbent assay (ELISA). Blue latex beads (2.5% solution of 0.3 microm) were coated with 1 mg/ml of GM1, GD1b, GQ1b or GM2. Aliquots (4 microl) of serum and the ganglioside-coated particles were mixed and rocked on a glass slide for 30 to 40 seconds. The reaction was observed under a microscope and compared with the antiganglioside antibody titers determined with ELISA.. Agglutination was strong in sera of which the IgM or IgG titers of anti-GM1, GD1b, GQ1b or GM2 antibodies were found to be more than 1:6,400 on ELISA except for 2 samples, but weak or absent in sera with titers of 1:3,200. Agglutination was absent in sera of which the antibody titers were less than 1:3,200 on ELISA.. We could rapidly detect serum IgM and IgG anti-GM1, GD1b, GQ1b and GM2 antibodies in patients with GBS by means of the latex agglutination assay when sera exhibited high titers of the respective antibodies on ELISA. The sensitivity of our agglutination assay was much lower than that of ELISA.

Topics: Antibodies, Anti-Idiotypic; Cohort Studies; Enzyme-Linked Immunosorbent Assay; Female; G(M1) Ganglioside; G(M2) Ganglioside; Guillain-Barre Syndrome; Humans; Japan; Latex Fixation Tests; Male; Retrospective Studies; Sensitivity and Specificity

Topics: Acute Disease; Autoantibodies; Female; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Middle Aged; Vocal Cord Paralysis

To clarify the clinical features of patients with anti-GM1b antibody, we retrospectively investigated which conditions were associated with anti-GM1b antibody in a large number of patients. Two hundred out of 1,713 patients had anti-GM1b antibody. One hundred and sixty-six (83%) were diagnosed with Guillain-Barré syndrome (GBS) or atypical GBS with preserved deep tendon reflexes. Our study suggests that the anti-GM1b antibody testing is useful for supporting the diagnosis of GBS. In addition, anti-GM1b antibody was detected in 18 patients with Fisher syndrome and the related conditions associated with anti-GQ1b IgG antibody, and 3 patients with ataxic GBS associated with anti-GD1b IgG antibody.

Topics: Adult; Aged; Autoantibodies; Biomarkers; Female; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Immunoglobulin M; Male; Miller Fisher Syndrome; Retrospective Studies

GM(1)- and GD(1a)-like ganglioside mimicry in Campylobacter jejuni lipooligosaccharide (LOS) is considered to be involved in the pathogenesis of Campylobacter-induced Guillain-Barré syndrome (GBS). Compared with gastroenteritis-related isolates, GBS-related C. jejuni isolates were strongly associated with the expression of GD(1a)-like mimicry. The presence of a few genes involved in LOS ganglioside mimicry, cst-II, cgtA, and cgtB, was also associated with GBS-related strains. GD(1a)-like epitope expression may be an important virulence phenotype associated with the risk of developing GBS following campylobacter infection.

Topics: Antigens, Bacterial; Base Sequence; Campylobacter jejuni; DNA, Bacterial; Epitopes; G(M1) Ganglioside; Gangliosides; Gene Expression; Genes, Bacterial; Guillain-Barre Syndrome; Humans; Lipopolysaccharides; Molecular Mimicry; Risk Factors; Virulence

Topics: Antibodies, Anti-Idiotypic; Chronic Disease; Demyelinating Diseases; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Odds Ratio; Polyneuropathies; Predictive Value of Tests; Sensitivity and Specificity

Topics: Autoantibodies; Campylobacter Infections; Campylobacter jejuni; Enteritis; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans

A 21-year-old man developed rapid progression of tetraplegia, bulbar palsy, and respiratory paralysis after Campylobacterjejuni enteritis. Based on the diagnosis of Guillain-Barré syndrome, he received plasmapheresis and intravenous immunoglobulin. Serum anti-GT1a IgG antibody which lacked cross-reactivity with GQ1b was detected. Four months after the onset, the patient still had severe muscle weakness of the lower limbs. This case suggests that anti-GT1a IgG antibody can be associated with severe paralysis in Guillain-Barré syndrome after C. jejuni enteritis.

Topics: Adult; Autoantibodies; Campylobacter Infections; Campylobacter jejuni; Enteritis; Enzyme-Linked Immunosorbent Assay; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Immunoglobulin M; Immunoglobulins, Intravenous; Male; Plasmapheresis; Treatment Outcome

Sera from 40 patients with Guillain-Barré syndrome (GBS), including the subtypes acute inflammatory demyelinating polyneuropathy (AIDP), acute motor axonal neuropathy (AMAN), acute motor and sensory axonal neuropathy (AMSAN), and Miller Fisher syndrome (MFS) were examined for the presence of anti-ganglioside antibodies using the ganglioside agglutination assay, and the enzyme-linked immunosorbent assay (ELISA). In the ELISA system, sera were tested for IgM and IgG antibodies to GM1, GM2, GD1a, GD1b, GT1b, and GQ1b gangliosides. Antibodies to gangliosides were detected in 21 (53%) of the GBS patients by agglutination assay and in 17 (43%) of the patients by ELISA. Some of the sera reacted with more than one ganglioside. Antibodies were not found in the control sera that were studied. The agglutination assay may be useful for rapid screening of GBS sera for antibodies to multiple gangliosides.

Topics: Agglutination Tests; Antibodies; Axons; Enzyme-Linked Immunosorbent Assay; G(M1) Ganglioside; G(M2) Ganglioside; Gangliosides; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Immunoglobulin M; Peripheral Nerves; Reproducibility of Results

A 36-year-old woman presented acute polyradiculoneuropathy following Chlamydia pneumoniae infection. Although electrophysiologic studies were normal, clinical features were typical of Guillain-Barré syndrome (GBS). Anti-ganglioside GM1 antibodies were positive. Two other cases of GBS following Chlamydia pneumoniae infection have been reported, but no specific feature emerges. Outcome was good in our patient after intravenous globulin then antibiotic therapy. Our case supports the notion that Chlamydia pneumoniae infection can induce GBS. The association is probably underestimated.

Topics: Adult; Antibodies, Bacterial; Autoantibodies; Autoimmune Diseases; Chlamydophila Infections; Chlamydophila pneumoniae; Female; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Immunoglobulin M; Immunoglobulins, Intravenous; Mycoplasma pneumoniae; Pneumonia, Bacterial; Tetracyclines

Elevated titers of serum anti-GM(1) antibodies of IgG isotype are found frequently in patients with Guillain-Barré syndrome. Much evidence indicates that these autoantibodies are involved in disease progression, but their exact function and the mechanism of their appearance are still unclear. In an attempt to reproduce "ganglioside syndrome", the experimental model of neuropathy developed by Nagai et al. (Neurosci. Lett. 2 (1976) 107), rabbits were intensively immunized with GM(1) in complete Freund adjuvant (CFA). High titers of anti-GM(1) antibodies were produced, with class switch and affinity maturation indicating an elaborate immune response. Unexpectedly, the rabbits did not show any clinical symptoms of neuropathy. Relatively affinities of both IgM and IgG antibodies were significantly lower than those of similar antibodies from neuropathy patients. These results suggest the existence of a threshold value above which affinity of anti-GM(1) antibodies becomes an important factor in disease induction. The absence of neuropathy symptoms in rabbits may be explained by absence of these high-affinity anti-GM(1) antibodies.

Topics: Animals; Antibody Affinity; Antigens, Helminth; Autoantibodies; Binding Sites, Antibody; Causality; G(M1) Ganglioside; Gangliosides; Glycosphingolipids; Guillain-Barre Syndrome; Helminth Proteins; Humans; Immunoglobulin G; Immunoglobulin M; Membrane Proteins; Molecular Structure; Peripheral Nerves; Protein Binding; Rabbits

Campylobacter jejuni infections are thought to induce antiganglioside antibodies in patients with Guillain-Barré syndrome (GBS) and Miller Fisher syndrome (MFS) by molecular mimicry between C. jejuni lipopolysaccharides (LPS) and gangliosides. We used purified LPS fractions from five Campylobacter strains to induce antiganglioside responses in rabbits. The animals that received injections with LPS from GBS-associated strains developed anti-GM1 and anti-GA1 antibodies. Animals injected with LPS from one MFS-related C. jejuni strain produced anti-GQ1b antibodies. Rabbits that were injected with Penner O:3 LPS had a strong anti-LPS response, but no antiganglioside reactivity was observed. The antiganglioside specificity in the rabbits reflected the specificity in the patients from whom the strains were isolated. In conclusion, our results indicate that an immune response against GBS- and MFS-associated C. jejuni LPS results in antiganglioside antibodies. These results provide strong support for molecular mimicry as a mechanism in the induction of antiganglioside antibodies following infections.

Topics: Adult; Animals; Antibodies, Bacterial; Campylobacter jejuni; Child; Epitopes; G(M1) Ganglioside; Gangliosides; Guillain-Barre Syndrome; Humans; Immunization; Lipopolysaccharides; Male; Middle Aged; Miller Fisher Syndrome; Rabbits

Topics: Adult; Antibodies, Anti-Idiotypic; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Male; Neural Conduction; Plasmapheresis

To examine whether Guillain-Barré syndrome (GBS) can be classified in clinical and immunological subgroups based on the type of prior illness. Background - The existence of antecedent symptoms supports the diagnosis of GBS in patients who experience acute muscle weakness progression. However, little is known about additional meanings of determining antecedent symptoms.. Prospective investigation of prior infectious illness in GBS and related disorders (n=176).. The frequent antecedent symptoms in GBS and related disorders were fever (52%), cough (48%), sore throat (39%), nasal discharge (30%), and diarrhea (27%). Patients who had sore throats or coughs frequently had ophthalmoparesis (respectively P=0.0004, P=0.001) and IgG anti-GQ1b antibody (P=0.01, P=0.007). Fever was associated with bulbar palsy (P=0.047) and headache with facial palsy (P=0.04). Patients with diarrhea often had anti-ganglioside IgG (anti-GM1 [P=0.0006] and anti-GM1b [P=0.008]), IgM (anti-GM1 [P=0.03], anti-GM1b [P=0.02], and anti-GalNAc-GD1a [P=0.047]) antibodies and rarely showed ophthalmoparesis or bulbar palsy (respectively P=0.02, P=0.04). Diarrhea and abdominal pain were closely associated with Campylobacter jejuni serology (respectively P<0.0001, P=0.01), whereas other symptoms were not related to pathogens such as cytomegalovirus, Epstein-Barr virus, or Mycoplasma pneumoniae.. Our comprehensive study showed that GBS preceded by sore throat, cough, fever, headache, or diarrhea respectively forms clinical or serological subgroups, or both. This association is not necessarily dependent on infection by the known trigger pathogens.

Topics: Adolescent; Adult; Aged; Child; Child, Preschool; Cough; Diagnosis, Differential; Diarrhea; Female; Fever; G(M1) Ganglioside; Guillain-Barre Syndrome; Headache; Humans; Immunoglobulin G; Male; Middle Aged; Pharyngitis; Prognosis; Prospective Studies; Serologic Tests

Topics: Animals; Antibodies; Antibody Specificity; Cattle; Disease Models, Animal; G(M1) Ganglioside; Guillain-Barre Syndrome; Immunization; Peripheral Nerves; Phenotype; Rabbits

Some humans develop the axonal form of Guillain-Barré syndrome after receiving bovine brain ganglioside. On sensitization with the ganglioside mixture, all of a group of rabbits injected developed high anti-GM1 IgG antibody titers, flaccid limb weakness of acute onset, and a monophasic illness course. Pathological findings for the peripheral nerves showed predominant Wallerian-like degeneration, with neither lymphocytic infiltration nor demyelination. IgG was deposited on the axons of the anterior roots, and GM1 was proved to be present on the axons of peripheral nerves. Sensitization with purified GM1 also induced axonal neuropathy, indicating that GM1 was the immunogen in the mixture. A model of human axonal Guillain-Barré syndrome has been established that uses inoculation with a bovine brain ganglioside mixture or isolated GM1. This model may help to clarify the molecular pathogenesis of the syndrome and to develop new treatments for it.

Topics: Animals; Antibodies; Antibody Specificity; Autoantibodies; Axons; Cattle; Chemotaxis, Leukocyte; Disease Models, Animal; G(M1) Ganglioside; Guillain-Barre Syndrome; Immunization; Immunoglobulin G; Immunoglobulin M; Immunohistochemistry; Male; Muscle Weakness; Peripheral Nerves; Rabbits; Wallerian Degeneration

The cross reactivity of anti-GM1 IgG antibody with various gangliosides and asialo-GM1 in serum samples from 27 patients with Guillain-Barré syndrome was investigated. An enzyme linked immunosorbent assay (ELISA) absorption study showed that anti-GM1 IgG antibody cross reacted with asialo-GM1 in 52% of the patients, GM1b in 41%, GD1b in 22%, and GalNAc-GD1a in 19%, and that it did not cross react with GM2, GT1b, or GQ1b. The antibody that cross reacted with GD1b was associated with a high frequency of cranial nerve involvement and negative Campylobacter jejuni serology. Anti-GM1 IgG antibody has a broad range of cross reactivity which may contribute to various clinical variations of Guillain-Barré syndrome.

Topics: Adult; Cross Reactions; Enzyme-Linked Immunosorbent Assay; Female; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Male; Middle Aged

IgG anti-ganglioside antibodies are present in a proportion of patients with the Guillain-Barré syndrome (GBS). To determine if antibodies to gangliosides are restricted in IgG subclass distribution, we evaluated IgG subclass antibody responses to gangliosides in sera of patients with GBS. Sera from GBS patients with IgG activity against gangliosides were analyzed for IgG subclass distribution using an enzyme-linked immunosorbent assay. The anti-LM1 antibodies in sera from GBS patients were predominantly of the IgG3 subclass while anti-GM1 and anti-GT1a antibodies were predominantly of the IgG1 and IgG3 subclasses. The results indicate a Th2-dependent antibody response.

Topics: Autoantibodies; Enzyme-Linked Immunosorbent Assay; G(M1) Ganglioside; Gangliosides; Guillain-Barre Syndrome; Humans; Immunoglobulin G

Elevated anti-ganglioside antibody levels mainly of anti-GM1 and anti-GD1a specificities have been reported in THE serum of patients with Guillain-Barré syndrome (GBS). The relevance of anti-ganglioside antibodies other than anti-GM1 and anti-GD1a IgG antibodies and the temporal profile of anti-ganglioside antibodies in GBS is less clear. We studied serum antibodies to GM1, GD1a, GD1b, GQ1b, sulfatide and cardiolipin of the IgM, IgG and IgA classes over the course of GBS in patients who were untreated or treated with high dose intravenous immunoglobulin (IvIg). Antibodies to GD1b, GQ1b, sulfatide and cardiolipin were not detected in the sera of the GBS patients examined in this study. Anti-GM1 IgG titers peaked around 40 days and anti-GD1a IgM around 90 days after GBS onset. Titers of anti-GM1 IgG antibodies decreased following IvIg treatment. Patients with antibody peaks, defined as fivefold or higher increase in antibody titer compared to the lowest antibody titer over the course of GBS, had higher disability scores during the first two weeks of GBS and a worse clinical outcome (anti-GM1 IgG and anti-GD1a IgM antibody peaks) and axonal damage (anti-GD1a IgM antibody peaks), compared to patients without peak antibody titers. Anti-GM1 IgG and anti-GD1a IgM antibodies are thus strongly associated with more severe- and predominantly axonal cases of GBS. The appearance of anti-GM1 IgG and anti-GD1a antibody peaks in the serum after the termination of the acute phase of GBS suggests that these antibodies are produced secondary to nerve damage in GBS. The data does not exclude the possibility that secondarily secreted anti-GM1 IgG and anti-GD1a IgM antibodies may themselves be biologically active and play a role in disease propagation and/or recovery from disease in some patients with GBS.

Topics: Antibodies; Axons; Cardiolipins; Disease Progression; Female; G(M1) Ganglioside; Gangliosides; Guillain-Barre Syndrome; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Immunoglobulins, Intravenous; Male; Middle Aged; Sulfoglycosphingolipids; Time Factors

To investigate whether antibodies are pathogenic in Guillain-Barré syndrome (GBS), we injected pre-treatment serum from 11 GBS patients intraperitoneally into rats in which the blood-nerve barrier had been opened by induction of mild adoptive transfer experimental autoimmune neuritis. There was no significant clinical, neurophysiological or pathological difference between rats receiving GBS serum compared with those receiving control serum, except that GBS serum caused minor excess weight loss. Murine monoclonal antibody to Campylobacter jejuni and gangliosides also did not exacerbate disease. This experiment failed to show antibody-mediated disease exacerbation and so does not support an antibody-mediated mechanism in GBS.

Topics: Animals; Antibodies, Bacterial; Antibodies, Monoclonal; Campylobacter; Campylobacter Infections; Cauda Equina; Demyelinating Diseases; Female; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Immunization, Passive; Immunoglobulin G; Immunoglobulin M; Neural Conduction; Neuritis, Autoimmune, Experimental; Rats; Rats, Inbred Lew; Reproducibility of Results; Severity of Illness Index; Spinal Nerve Roots; Weight Loss

Anti-ganglioside antibodies are consistently found in Guillain-Barré syndrome (GBS) patients from different geographical parts of the world. Several studies indicated differences in relative frequencies of anti-ganglioside reactivity and isotype distribution between GBS patients from Asia and from Europe. We investigated antibody reactivity against the gangliosides GM1, GM1b and GalNAc-GD1a in GBS patients from Japan and The Netherlands in two different laboratories. The proportion of GBS patients with anti-ganglioside antibodies did not differ between the two countries. GBS patients from The Netherlands more frequently had cross-reacting anti-GalNAc-GD1a/anti-GM1b antibodies and a stronger IgM anti-ganglioside response. Our findings indicate that geographical determined factors, dependent on either the host or the triggering infectious agent, determine the isotype distribution and fine specificity of anti-ganglioside antibodies in GBS patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antibody Specificity; Autoantibodies; Child; Cross Reactions; Enzyme-Linked Immunosorbent Assay; Female; G(M1) Ganglioside; Gangliosides; Guillain-Barre Syndrome; Humans; Japan; Male; Middle Aged; Netherlands; Seroepidemiologic Studies

Antiganglioside serum antibodies from a patient treated with gangliosides were examined for cross-reactivity with lipopolysaccharides (LPSs) of Campylobacter jejuni strains associated with Guillain-Barré syndrome (GBS). The patient had no preceding infection with C. jejuni and developed chronic progressive motor polyneuropathy following parenteral ganglioside treatment. Serum IgG antibodies recognised GM1 and GD1b gangliosides as well as asialo-GM1, and cross-reactivity was observed with LPSs from C. jejuni O:2, O:4, O:19 and O:41. The results give a clear indication that gangliosides and LPSs from C. jejuni serotypes associated with GBS share common epitopes.

Topics: Adult; Antibodies; Campylobacter jejuni; Cross Reactions; Female; G(M1) Ganglioside; Gangliosides; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Lipopolysaccharides; Polyneuropathies

To investigate the pathophysiology of selective absence of F waves and its relation with antiganglioside antibodies in Guillain-Barré syndrome (GBS). Some patients with GBS show the absence of F waves as an isolated conduction abnormality, which has been interpreted as demyelination in the proximal nerve segments.. In 62 consecutive patients with GBS, sequential nerve conduction and F wave studies were reviewed, and antibodies against ganglioside GM1, GM1b, GD1a, GalNAc-GD1a, GD1b, and GQ1b were measured by an enzyme linked immunosorbent assay.. In the first electrophysiological studies, isolated absence of F waves was found in 12 (19%) patients. Sequential studies in 10 of these patients showed two electrophysiological sequel patterns; rapid restoration of F waves (six patients), and persistent absence of F waves with distal motor nerve degeneration (acute motor axonal neuropathy, four patients). None of the 10 patients showed evidence of demyelination in the proximal, intermediate, or distal nerve segments throughout the course. Of the 62 patients, IgG antibodies against GM1, GM1b, GalNAc-GD1a, or GD1b were significantly associated with the electrodiagnosis of acute motor axonal neuropathy, and patients with these antibodies more often had isolated absence of F waves than patients without them (11 of 36 (31%) v one of 26 (4%); p<0.01). Eleven of the 12 patients with isolated absence of F waves had positive serology for one or more antiganglioside antibodies.. In GBS with antiganglioside antibodies, isolated absence of F waves is a frequent conduction abnormality especially in the early phase of the disease, and may be caused by axonal dysfunction, such as physiological conduction block or axonal degeneration at the nerve roots.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antibodies, Anti-Idiotypic; Axons; Child; Child, Preschool; Demyelinating Diseases; Electrophysiology; Enzyme-Linked Immunosorbent Assay; Female; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Male; Middle Aged; Motor Neurons; Nerve Degeneration; Neural Conduction; Peripheral Nerves; Time Factors

Lipopolysaccharides (LPS) from Campylobacter jejuni strains isolated from patients with Guillain-Barré syndrome (GBS) display molecular mimicry with GM1. We immunized rabbits with C. jejuni LPS from GBS-associated strains containing a GM1-like epitope. All animals produced high titre anti-LPS antibodies that were cross-reactive with GM1. We conclude that C. jejuni strains from GBS patients are able to induce antibodies that cross-react with gangliosides and LPS. This study further confirms the role of molecular mimicry in the induction of anti-ganglioside antibodies in GBS patients.

Topics: Animals; Antibodies; Antibody Formation; Campylobacter jejuni; Disease Models, Animal; Epitopes; G(M1) Ganglioside; G(M2) Ganglioside; Guillain-Barre Syndrome; Humans; Immunization; Immunoglobulin G; Immunoglobulin M; Lipopolysaccharides; Rabbits; Time Factors

GM1b is a minor ganglioside in human peripheral nerves. Serum anti-GM1b antibodies frequently are present in patients with Guillain-Barré syndrome (GBS). In this collaborative study, we investigated the antecedent infections, clinical features, and response to treatment of GBS patients with anti-GM1b antibodies. Of 132 GBS patients who participated in the Dutch GBS trial that compared the effect of intravenous immunoglobulins and plasma exchange, 25 (19%) patients had anti-GM1b antibodies. IgM antibodies were present in 14, IgG antibodies in 15, and both isotypes in 4 patients. The 25 patients with anti-GM1b antibodies had a clinical pattern distinct from that of the other 107 GBS patients. They more often had an episode of gastrointestinal illness and frequently showed serological evidence of recent infection by Campylobacter jejuni. The anti-GM1b-positive subgroup was marked by more rapidly progressive, more severe, and predominantly distal weakness. Cranial nerve involvement and sensory deficits were less common in the patients with anti-GM1b antibodies. The presence of anti-GM1b antibodies was associated with slower recovery. The clinical manifestations predominantly were associated with anti-GM1b antibodies of the IgG isotype. Fourteen (56%) of the 25 patients with anti-GM1b antibodies also had anti-GM1 antibodies. The group of patients with both antibodies was clinically more homogeneous and had a more rapidly progressive, pure motor neuropathy. The subgroup of anti-GM1b-positive GBS patients responded well to treatment with immunoglobulins but not to plasmapheresis. The distinctive clinical features of the patients with anti-GM1b antibodies show that acute motor neuropathy represents a specific subgroup within GBS and that recognizing these patients may have consequences as to the choice of therapy.

Topics: Adolescent; Adult; Aged; Antibodies; Electromyography; Female; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Immunoglobulins, Intravenous; Male; Middle Aged; Muscles

To determine the possible role of anti-GM1 ganglioside antisera from patients with Gullain-Barr*e syndrome (GBS) or chronic inflammatory demyelinating polyneuropathy (CIDP) in the development of nerve dysfunction.. The effect of the anti-GM1 antibody positive antisera obtained from 4 GBS patients and 1 CIDP patient on membrane potential and ionic currents in rat single myelinated nerve fibers was investigated using the voltage clamp technique and compared with that of the anti-GM1 negative antisera obtained from 3 healthy controls and 2 GBS patients.. In the presence of active complement, anti-GM1 positive antisera from 5 patients including 4 GBS patients and 1 CIDP patient significantly suppressed Na+ current more than anti-GM1 negative antisera.. This study supports the notion that anti-GM1 antibody is one of the causative factors of conduction abnormality in GBS patients.

Topics: Adult; Animals; Enzyme-Linked Immunosorbent Assay; Female; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Immune Sera; Male; Membrane Potentials; Middle Aged; Nerve Fibers, Myelinated; Patch-Clamp Techniques; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; Potassium Channels; Rats; Rats, Sprague-Dawley; Sodium; Sodium Channels

Some patients with Guillain-Barré syndrome (GBS) develop bulbar palsy, which may lead to serious complications during the acute phase of the illness. A serological marker that could predict the occurrence of bulbar palsy would be valuable for the treatment of acute GBS. We examined the serum levels of various IgG antiganglioside antibodies in the sera of 16 patients with GBS with bulbar palsy [GBS-BP(+)] and 72 patients with GBS without bulbar palsy [GBS-BP(-)]. Anti-GT1a antibodies were detected in a higher percentage of the GBS-BP(+) patients (10/16, 63%) than the GBS-BP(-) patients (2/72, 3%). In addition to GT1a, a new disialosylganglioside antigen was recognized by the sera of four GBS-BP(+) patients. Anti-GM1b antibodies were also frequently detected in the sera of the GBS-BP(+) cases. However, anti-GM1 and anti-GalNAc-GD1a antibodies, which are highly associated with acute axonal motor neuropathy (AMAN), were not detected in any of the GBS-BP(+) cases, while anti-GM1 antibodies were detected in 29% (21/72) and anti-GalNAc-GD1a antibodies were detected in 8% (6/72) of the GBS-BP(-) cases. These findings suggest that the presence of particular antiganglioside antibodies might be related with certain clinical manifestations of GBS. In patients who are diagnosed with GBS, the presence or absence of anti-GT1a and anti-GM1b antibodies should be tested at the early stage of GBS so that appropriate therapies that prevent the development of bulbar palsy and improve the outcome of GBS, may be initiated.

Topics: Adult; Aged; Bulbar Palsy, Progressive; Female; G(M1) Ganglioside; Gangliosides; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Male; Middle Aged

To investigate whether anti-GM2 antibodies in patients with Guillain-Barré syndrome (GBS) are induced by molecular mimicry with cytomegalovirus (CMV).. Antibodies against ganglioside GM2 are frequently present in the serum from GBS patients with an antecedent infection with CMV.. The authors detected inhibition of anti-GM2 reactivity after incubation of GM2-reactive serum samples with fibroblasts infected with a GBS-associated CMV strain. Control sera consisted of GQ1b-reactive samples, and control antigens included uninfected fibroblasts and fibroblasts that were infected with other herpes viruses.. Serum immunoglobulin M reactivity with GM2 was decreased in a dose-dependent manner after incubation with CMV-infected fibroblasts. Incubation of anti-GM2-positive serum samples with uninfected fibroblasts and fibroblasts infected with varicella zoster virus did not inhibit anti-GM2 reactivity, whereas this reactivity was slightly decreased after incubation with herpes simplex virus type 1 in one patient. Antibodies against ganglioside GQ1b did not react with CMV-infected fibroblasts.. CMV-infected fibroblasts express gangliosidelike epitopes that recognize specifically anti-GM2 antibodies. These results support the hypothesis that antiganglioside antibodies in CMV-infected GBS patients are induced by molecular mimicry between GM2 and antigens that are induced by a CMV infection.

Topics: Adult; Aged; Antibody Specificity; Autoantibodies; Cross Reactions; Cytomegalovirus; Cytomegalovirus Infections; Dose-Response Relationship, Immunologic; Enzyme-Linked Immunosorbent Assay; Female; Fibroblasts; G(M1) Ganglioside; G(M2) Ganglioside; Guillain-Barre Syndrome; Herpesvirus 1, Human; Herpesvirus 3, Human; Humans; Immunosorbent Techniques; Serologic Tests

We used an ELISA technique to measure IgG and IgM antibodies to the ganglioside GM1, with the results expressed in arbitrary units. We tested 1007 sera from patients with peripheral neuropathy or muscle weakness. For IgG and IgM antibodies, the distribution of results differed significantly from a normal distribution. In the patient group, 81 of 1007 sera had elevated levels of IgG antibodies (> 10 units). Of these, 11 patients had very high levels (> 50 units). These 11 patients had diagnoses of GBS (4), motor neurone disease (3) or non-specific idiopathic neuropathy (4). For IgM antibodies, 115 of 1007 sera were positive (> 20 units). Of these, 18 patients had very high levels (> 50 units). These 18 patients had diagnoses of Guillain-Barré syndrome or Miller Fisher syndrome (4), multifocal motor neuropathy (4), motor neurone disease (2), non-specific neuropathy (2). We conclude that anti-GM1 antibodies in high titre are uncommon. Patients with multifocal motor neuropathy have high levels of antibody. However, patients with other disorders may also have high levels, so that anti-GM1 antibody levels alone are not a specific test for multifocal motor neuropathy. We found that antibodies to GM1 were present in the sera of patients with chronic idiopathic neuropathy, leading us to suggest that these antibodies may sometimes arise as a secondary response to disease.

Topics: Adult; Aged; Aged, 80 and over; Autoantibodies; Biomarkers; Female; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Immunoglobulin M; Male; Middle Aged; Motor Neuron Disease; Peripheral Nervous System Diseases

The aim of this study was to examine the presence of antibodies to GM1 and sulfatide in various IVIg preparations. Five brands of commercially available human IVIg (Sandoglobulin, Isiven, Cytogam, Omrigam and Cutter) were examined and compared. Serial dilutions of each of the above preparations were prepared at a working range of 0.009 to 25.0 mg/ml IVIg, and screened by a standard 96-well microplate EIA for autoantibodies to the ganglioside GM1 and to the glycolipid sulfatide. The various IVIg preparations (Omrigam, Cytogam, Sandoglobulin, Isiven), except for Cutter IVIg, contained low to medium titers of the autoantibodies tested. Omrigam and Cytogam IVIg contained low titer of antibodies to GM1, and medium-titer of antibodies to sulfatide, whereas Sandoglobulin and Isiven contained only low-titer of autoantibodies to sulfatide. The presence of natural autoantibodies to myelin in human sera may explain the presence of the tested antibodies within IVIg preparations. Measurements of antibodies to ganglioside and glycolipid in sera of Guillain-Barré patients immediately following IVIg, would probably not reveal antibody decrease. Alternatively, long-term (several weeks) follow-up of titers might result in their modification due to inhibition of antibodies production by IVIg.

Topics: Autoantibodies; G(M1) Ganglioside; Guillain-Barre Syndrome; Humans; Immunoglobulins, Intravenous; Sulfoglycosphingolipids

It has been reported recently that Haemophilus influenzae can elicit an axonal form of Guillain-Barré syndrome. To investigate the incidence and features of H. influenzae-related Guillain-Barré syndrome, anti-H. influenzae antibody titres were measured by enzyme-linked immunosorbent assay (ELISA) in 46 consecutive Japanese patients with Guillain-Barré syndrome, 49 normal controls, 24 patients with multiple sclerosis and 27 patients with amyotrophic lateral sclerosis (ALS). Whole bacteria of non-encapsulated (non-typable) H. influenzae isolated from one of the Guillain-Barré syndrome patients was the antigen used. Elevated anti-H. influenzae antibodies for two or three classes of IgG, IgM and IgA were found in six (13%) Guillain-Barré syndrome patients, but not in the normal controls and patients with multiple sclerosis or ALS. The incidence was significantly higher in patients with Guillain-Barré syndrome than in the normal controls (P = 0.01) and patients with multiple sclerosis or ALS (P = 0.009). Western blot analysis confirmed that the H. influenzae-positive patients' IgG recognized the lipopolysaccharides of H. influenzae. Guillain-Barré syndrome patients with anti-H. influenzae antibodies showed relatively uniform clinical and laboratory features: prodromal respiratory infection, less frequent cranial and sensory nerve involvement, pure motor axonal degeneration on electrophysiology, and positivity for IgG anti-GM1 antibodies. Although the features were similar to those in Guillain-Barré syndrome patients infected by Campylobacter jejuni, the recoveries seemed to be better in patients with H. influenzae-related Guillain-Barré syndrome. It is concluded that a form of Guillain-Barré syndrome occurs after respiratory infection by H. influenzae in the Japanese population. A particular strain of non-typable H. influenzae has a ganglioside GM1-like structure and elicits axonal Guillain-Barré syndrome similar to C. jejuni-related Guillain-Barré syndrome.

Topics: Adult; Aged; Aged, 80 and over; Amyotrophic Lateral Sclerosis; Antibodies, Bacterial; Autoantibodies; Axons; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Female; G(M1) Ganglioside; Guillain-Barre Syndrome; Haemophilus Infections; Haemophilus influenzae; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Male; Multiple Sclerosis; Retrospective Studies

A 68-year-old man, with Hairy Cell Leukemia developed a Guillain-Barré syndrome (G-B), 32 days after a single course of 2-Chlorodeoxyadenosine (CDA) at 0,14 mg/k/d, for five days in a two-hour-i.v. infusion and following a febrile neutropenia episode. In order to clarify whether this G-B case was related to an infection or to CDA neurotoxicity, we screened for infection-related autoimmune G-B and for antibodies (abs.) against gangliosides of peripheral nerves. Blood and urinary cultures were negative as well as serum anti-virus abs. However, serum anti-ganglioside abs. were positive for anti-asialo GM1 and anti-Gd1b. This latter finding was consistent with an autoimmune mechanism, not described until now as CDA neurotoxicity. In the present case, we do not have enough evidence to link CDA administration to the G-B syndrome. We think that it is necessary to exclude other causes of neurotoxicity before considering CDA adverse effect.

Topics: Aged; Autoantibodies; Cladribine; G(M1) Ganglioside; Gangliosides; Guillain-Barre Syndrome; Humans; Leukemia, Hairy Cell; Male

Griffin and colleagues (Griffin JW, Li CY, Ho TW, Tian M, Gao CY, Xue P, Mishu B, Cornblath DR, Macko C, McKhann GM, Asbury AK. Pathology of motor-sensory axonal Guillain-Barré syndrome. Ann Neurol 1996;39:17-28 [4]) proposed that acute motor axonal neuropathy (AMAN) and acute motor-sensory axonal neuropathy (AMSAN) are part of the spectrum of a single type of immune attack on the axon. In contrast, IgG anti-GM1 antibody is associated closely with AMAN, but whether other IgG anti-ganglioside antibodies are associated with this neuropathy is not clear. We investigated whether IgG anti-ganglioside antibodies can be used as immunological markers to differentiate AMAN from acute inflammatory demyelinating polyneuropathy (AIDP) and whether these autoantibodies are present in AMSAN. The frequencies of anti-GM1, anti-GM1b, and anti-GD1a IgG antibodies in 21 AMAN patients were significantly higher than in 19 AIDP patients. Anti-GM1b and anti-GD1a IgG, as well as anti-GM1 IgG antibodies, therefore are immunological markers for AMAN. The patients with AMSAN had anti-GM1, anti-GM1b, and anti-GD1a IgG antibodies, indicative that AMAN and AMSAN share a common immunological profile.

Topics: Adolescent; Adult; Aged; Antibodies, Bacterial; Autoantibodies; Campylobacter jejuni; Child; Female; G(M1) Ganglioside; Gangliosides; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Male; Middle Aged; Neural Conduction; Predictive Value of Tests

To investigate the presence of anti-GalNAc-GD1a antibodies in patients with Guillain-Barré syndrome (GBS) and to determine the relation of anti-ganglioside antibodies with clinical features.. The GBS is heterogeneous with regard to clinical manifestations, antecedent infections, and the presence and specificity of anti-ganglioside antibodies. Recently, antibodies to minor gangliosides have been identified in serum from GBS patients.. The authors used ELISA to detect anti-ganglioside antibodies in 132 GBS patients and then correlated results with a database containing information on antecedent infections and clinical parameters.. Anti-GalNAc-GD1a antibodies could be detected in 19 (14%) GBS patients. The presence of anti-GalNAc-GD1a antibodies was related to antecedent Campylobacter jejuni infection (p<0.001). GBS patients with anti-GalNAc-GD1a antibodies had a rapidly progressive, more severe, and predominantly distal weakness. Furthermore, they had less sensory loss, paresthesia, and cranial nerve involvement. In most patients, this reactivity was independent of reactivity to GM1. Dividing patients into separate groups based on their reactivity to GalNAc-GD1a and GM1 enabled the authors to delineate more homogeneous subgroups with regard to clinical features.. This study provides further evidence for the hypothesis that antecedent infections and the specificity of subsequent anti-neural antibody responses determine the clinical manifestations in GBS patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Autoantibodies; Autoimmune Diseases of the Nervous System; Campylobacter Infections; Campylobacter jejuni; Child; Child, Preschool; Enzyme-Linked Immunosorbent Assay; Female; G(M1) Ganglioside; Gangliosides; Guillain-Barre Syndrome; Humans; Male; Middle Aged; Neurologic Examination