ganglioside--gd1a and Guillain-Barre-Syndrome

Guillain-Barré Syndrome (GBS) is an acute monophasic immune-mediated neuropathy, generally considered to be of good prognosis. However, 15-20% of GBS patients cannot walk independently at six months from onset. Poor prognostic factors for long-term functional disability included old age, preceding diarrhea, muscle weakness on admission and on day 7 from admission, severe GBS disability score at two weeks from admission and IgG antibody against GD1a/GD1b ganglioside complex. Factors related with requirement of mechanical ventilation included the time from onset to admission <7 days, muscle weakness on admission, facial and/or bulbar weakness and IgG antibody against GQ1b. Recently modified Erasmus GBS outcome score (mEGOS) and Erasmus GBS respiratory insufficiency score (EGRIS) were reported as prognostic factors for the long-term functional disability and respiratory insufficiency. Those were designed on Dutch patients. The usefulness of these tools in Japan or other countries remained unknown. The authors validated mEGOS and EGRIS on Japanese GBS patients in Japanese GBS outcome study, which revealed that these tools were also adaptable on Japanese GBS patients. To identify clinical and biological factors of GBS in more detail, such a large scale prospective study as International GBS outcome study (IGOS) is warranted.

Topics: Antibodies; Gangliosides; Guillain-Barre Syndrome; Humans; Prognosis; Severity of Illness Index

Serum antibodies to different gangliosides have been identified in some Guillain-Barré (GBS) subtypes and variants. In the January issue of Experimental Neurology Susuki and colleagues (2012) showed that in experimental neuropathies associated with antibodies to GM1, GD1a and GD1b the common mechanism is a complement mediated dysfunction and disruption of the nodes of Ranvier which causes a pathophysiological continuum from early reversible conduction failure to axonal degeneration. These observations, correlated and integrated with electrophysiological and pathological findings in humans indicate that the GBS subtypes acute motor conduction block neuropathy, acute motor axonal neuropathy, acute motor and sensory neuropathy and acute sensory neuropathy and possibly also a chronic disorder as multifocal motor neuropathy represent a spectrum of the same immunopathologic process. Being the nodal axolemma and the paranode the focus of the nerve injury, these immune mediated neuropathies could be more properly classified as nodo-paranodopathies.

Topics: Animals; Autoantibodies; Gangliosides; Guillain-Barre Syndrome; Humans; Polyneuropathies; Sphingolipid Activator Proteins

Topics: Adolescent; Adult; Autoantibodies; Autoantigens; Autoimmune Diseases of the Nervous System; Campylobacter Infections; Campylobacter jejuni; Enteritis; Gangliosides; Guillain-Barre Syndrome; Humans; Molecular Mimicry; Siblings

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

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

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

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

Immunoglobulin G (IgG) anti-GD1a ganglioside antibody is an important marker of Guillain-Barré syndrome (GBS). This antibody is highly associated with disease severity, the need for mechanical ventilation, and axonal degeneration of peripheral nerves. We report a 46-year-old female patient manifesting the IgG anti-GD1a antibody with polycranial neuropathy and sensory ataxia as a variant of GBS. She presented with slurred speech, swallowing difficulties, and gait disturbance following diarrhea. Decreased sensations of vibration and position were found in her distal limbs and she had an ataxic gait with a positive Romberg sign. Her serum was positive for IgG anti-GD1a ganglioside antibody (1:640). Her neurological examination at the third month after intravenous Ig treatment showed complete recovery.

Topics: Ataxia; Autoantibodies; Autoantigens; Cranial Nerve Diseases; Enzyme-Linked Immunosorbent Assay; Female; Gangliosides; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Middle Aged

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

Topics: Adult; Autoantibodies; Autoantigens; Female; Gangliosides; Guillain-Barre Syndrome; Humans; Recurrence

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

A patient with acute purely motor polyneuropathy with positive GD1a ganglioside antibodies who presented with paresis in combination with hyperreflexia is reported. Neurophysiological tests revealed features compatible with acute motor axonal neuropathy. Therapy with intravenous immunoglobulin led to rapid clinical improvement. However, at the time when signs of active denervation appeared on electromyographic testing, the patient developed bilateral papillitis. The pathogenesis of pure motor Guillain-Barré syndrome with hyperreflexia and papillitis is discussed.

Topics: Antibodies; Electromyography; Gangliosides; Guillain-Barre Syndrome; Humans; Male; Middle Aged; Papilledema; Reflex, Abnormal

The motor axonal variant of Guillain-Barré syndrome is associated with anti-GD1a immunoglobulin antibodies, which are believed to be the pathogenic factor. In previous studies we have demonstrated the motor terminal to be a vulnerable site. Here we show both in vivo and ex vivo, that nodes of Ranvier in intramuscular motor nerve bundles are also targeted by anti-GD1a antibody in a gradient-dependent manner, with greatest vulnerability at distal nodes. Complement deposition is associated with prominent nodal injury as monitored with electrophysiological recordings and fluorescence microscopy. Complete loss of nodal protein staining, including voltage-gated sodium channels and ankyrin G, occurs and is completely protected by both complement and calpain inhibition, although the latter provides no protection against electrophysiological dysfunction. In ex vivo motor and sensory nerve trunk preparations, antibody deposits are only observed in experimentally desheathed nerves, which are thereby rendered susceptible to complement-dependent morphological disruption, nodal protein loss and reduced electrical activity of the axon. These studies provide a detailed mechanism by which loss of axonal conduction can occur in a distal dominant pattern as observed in a proportion of patients with motor axonal Guillain-Barré syndrome, and also provide an explanation for the occurrence of rapid recovery from complete paralysis and electrophysiological in-excitability. The study also identifies therapeutic approaches in which nodal architecture can be preserved.

Topics: Animals; Autoantibodies; Axons; Binding Sites, Antibody; Calpain; Complement Activation; Gangliosides; Guillain-Barre Syndrome; Male; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Mice, Knockout; Mice, Transgenic; Motor Neurons; Ranvier's Nodes

The acute motor axonal neuropathy (AMAN) variant of Guillain-Barré syndrome (GBS) is associated with anti-GD1a and anti-GM1 IgG antibodies. The basis of preferential motor nerve injury in this disease is not clear, however, because biochemical studies demonstrate that sensory and motor nerves express similar quantities of GD1a and GM1 gangliosides. To elucidate the pathophysiology of AMAN, we have developed several monoclonal antibodies (mAbs) with GD1a reactivity and reported that one mAb, GD1a-1, preferentially stained motor axons in human and rodent nerves. To understand the basis of this preferential motor axon staining, several derivatives of GD1a were generated by various chemical modifications of N-acetylneuraminic (sialic) acid residues (GD1a NeuAc 1-amide, GD1a NeuAc ethyl ester, GD1a NeuAc 1-alcohol, GD1a NeuAc 1-methyl ester, GD1a NeuAc 7-alcohol, GD1a NeuAc 7-aldehyde) on this ganglioside. Binding of anti-GD1a mAbs and AMAN sera with anti-GD1a Abs to these derivatives was examined. Our results indicate that mAbs with selective motor axon staining had a distinct pattern of reactivity with GD1a-derivatives compared to mAbs that stain both motor and sensory axons. The fine specificity of the anti-GD1a antibodies determines their motor selectivity, which was validated by cloning a new mAb (GD1a-E6) with a chemical and immunocytochemical binding pattern similar to that of GD1a-1 but with two orders of magnitude higher affinity. Control studies indicate that selective binding of mAbs to motor nerves is not due to differences in antibody affinity or ceramide structural specificity. Since GD1a-reactive mAb with preferential motor axon staining showed similar binding to sensory- and motor nerve-derived GD1a in a solid phase assay, we generated computer models of GD1a based on binding patterns of different GD1a-reactive mAbs to different GD1a-derivatives. These modelling studies suggest that critical GD1a epitopes recognized by mAbs are differentially expressed in motor and sensory nerves. The GD1a-derivative binding patterns of AMAN sera resembled those with motor-specific mAbs. On the basis of these findings we postulate that both the fine specificity and ganglioside orientation/exposure in the tissues contribute to target recognition by anti-ganglioside antibodies and this observation provides one explanation for preferential motor axon injury in AMAN.

Topics: Antibodies, Monoclonal; Antibody Specificity; Antigen-Antibody Reactions; Autoantibodies; Axons; Fatty Acids; Gangliosides; Guillain-Barre Syndrome; Humans; Models, Molecular; Motor Neurons; Neuraminidase; Structure-Activity Relationship

Topics: Adult; Gangliosides; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Male

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

Anti-GD1a ganglioside antibodies (Abs) are the serological hallmark of the acute motor axonal form of the post-infectious paralysis, Guillain-Barre syndrome. Development of a disease model in mice has been impeded by the weak immunogenicity of gangliosides and the apparent resistance of GD1a-containing neural membranes to anti-GD1a antibody-mediated injury. Here we used mice with altered ganglioside biosynthesis to generate such a model at motor nerve terminals. First, we bypassed immunological tolerance by immunizing GD1a-deficient, beta-1,4-N-acetylgalactosaminyl transferase knock-out mice with GD1a ganglioside-mimicking antigens from Campylobacter jejuni and generated high-titer anti-GD1a antisera and complement fixing monoclonal Abs (mAbs). Next, we exposed ex vivo nerve-muscle preparations from GD1a-overexpressing, GD3 synthase knock-out mice to the anti-GD1a mAbs in the presence of a source of complement and investigated morphological and electrophysiological damage. Dense antibody and complement deposits were observed only over presynaptic motor axons, accompanied by severe ultrastructural damage and electrophysiological blockade of motor nerve terminal function. Perisynaptic Schwann cells and postsynaptic membranes were unaffected. In contrast, normal mice were not only unresponsive to immunization with GD1a but also resistant to neural injury during anti-GD1a Ab exposure, demonstrating the central role of membrane antigen density in modulating both immune tolerance to GD1a and axonal susceptibility to anti-GD1a Abmediated injury. Identical paralyzing effects were observed when testing mouse and human anti-GD1a-positive sera. These data indicate that anti-GD1a Abs arise via molecular mimicry and are likely to be clinically relevant in injuring peripheral nerve axonal membranes containing sufficiently high levels of GD1a.

Topics: Animals; Antigens, Bacterial; Autoantibodies; Autoantigens; Axons; Campylobacter jejuni; Complement Activation; Disease Models, Animal; Gangliosides; Guillain-Barre Syndrome; Immune Tolerance; Immunization; Male; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Mice, Knockout; Molecular Mimicry; Motor Neurons; N-Acetylgalactosaminyltransferases; Nervous System Autoimmune Disease, Experimental; Neuromuscular Junction; Polypeptide N-acetylgalactosaminyltransferase; Sialyltransferases

Guillain-Barré syndrome (GBS), an autoimmune disease of the peripheral nervous system, is associated with antecedent Campylobacter jejuni infection. GM and KM allotypes--genetic markers of immunoglobulin gamma and kappa chains, respectively--are implicated in the etiopathogenesis of several autoimmune diseases. To determine if GM/KM phenotypes are associated with GBS and influence antibody responses to C. jejuni and to GM1 and GD1a gangliosides, 72 Japanese GBS patients and 73 controls were allotyped for several GM and KM markers. Sera from patients were characterized for antibodies to C. jejuni, GM1, and GD1a. The distribution of KM phenotypes was significantly different in patients with anti-GD1a ganglioside antibodies from those who lacked these antibodies (P=0.029). No other significant associations were found. These results suggest that KM allotypes are not risk factors for developing GBS, but contribute significantly to the generation of autoimmune responses to GD1a ganglioside in patients with this disease.

Topics: Campylobacter Infections; Gangliosides; Genetic Predisposition to Disease; Guillain-Barre Syndrome; Humans; Immunoglobulin gamma-Chains; Immunoglobulin kappa-Chains; Immunoglobulin Km Allotypes; Immunoglobulins; Japan; Linkage Disequilibrium; Models, Statistical; Phenotype

Antibodies specific for a complex of gangliosides GD1a and GD1b (GD1a/GD1b) were found in sera from eight of 100 patients with Guillain-Barre syndrome (GBS) by the use of enzyme-linked immunosorbent assay and thin-layer chromatogram immunostaining. Those sera also had antibody activities to such ganglioside complexes as GD1a/GM1, GD1b/GT1b, and GM1/GT1b but had little or no reactivity to the each isolated antigen. Clustered epitopes of the ganglioside complex in the plasma membrane may be targeted by such an antibody, and interaction between the antibody and ganglioside complex may induce the neuropathy.

Topics: Adult; Aged; Antibodies; Chromatography, Thin Layer; Enzyme-Linked Immunosorbent Assay; Female; Gangliosides; Gangliosidoses; Guillain-Barre Syndrome; Humans; Immunoblotting; Male; Middle Aged

Topics: Adult; Ataxia; Facial Paralysis; Gangliosides; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Immunotherapy; Infections; Male; Plasmapheresis

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

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

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

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

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