g(m1)-ganglioside and Enteritis

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

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

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

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

The relationship between preceding infections and antibodies to glycolipids was investigated in 205 Japanese patients with Guillain-Barré syndrome (GBS). Serological evidence of recent Campylobacter jejuni (C. jejuni) infection was found in 45% of the patients, compared with 1% in healthy controls. In contrast, recent infection of cytomegalovirus (CMV), Mycoplasma pneumoniae (M. pneumoniae) and Epstein-Barr virus (EBV) was detected in only 5%, 2% and none of the patients, respectively. C. jejuni-associated GBS was more frequent in early spring than in other seasons. All stool specimens positive for C. jejuni isolation were obtained within 10 days after the onset of GBS symptoms. Of 13 C. jejuni isolates from GBS patients, 10 (77%) belonged to Penner serotype 19 (heat-stable, HS-19). Elevated titers of anti-GM1 antibody were found in 8 (80%) of 10 GBS patients whose C. jejuni isolates belonged to HS-19 and in none of those infected with non-HS-19 C. jejuni (P = 0.04), and in 49% of 92 patients with C. jejuni infection and 25% of patients without infection of C. jejuni, CMV, EBV, or M. pneumoniae (P = 0.0007). The frequencies of elevated antibody titers to GD1a, GD1b and GQ1b were also significantly higher in GBS patients associated with C. jejuni than those not associated with C. jejuni, CMV, EBV, and M. pneumoniae. GBS in Japan seems to be associated more frequently with C. jejuni and less frequently with CMV than in Europe and North America.

Topics: Adolescent; Adult; Aged; Antibodies, Bacterial; Antibodies, Viral; Antibody Specificity; Antigens, Bacterial; Autoantibodies; Autoimmune Diseases; Campylobacter Infections; Campylobacter jejuni; Child; Child, Preschool; Comorbidity; Cytomegalovirus Infections; Enteritis; Europe; Feces; Female; G(M1) Ganglioside; Galactosylceramides; Gangliosides; Herpesviridae Infections; Herpesvirus 4, Human; Humans; Japan; Male; Middle Aged; Molecular Mimicry; Mycoplasma pneumoniae; Pneumonia, Mycoplasma; Polyradiculoneuropathy; United States

IgA has an important function in the gastrointestinal immune system. We investigated IgA anti-ganglioside antibodies in Guillain-Barré syndrome (GBS) and Fisher's syndrome (FS) subsequent to Campylobacter jejuni enteritis. In previous studies, serological diagnosis of C. jejuni infection was based on the detection of IgG, IgA, and IgM anti-C. jejuni antibodies. Our study, however, showed that the detection of IgG anti-C. jejuni antibody alone was sufficient for the serological diagnosis of antecedent C. jejuni enteritis in GBS and FS, when the cut-off level was defined for results of sera from C. jejuni-isolated patients. Serological evidence of C. jejuni infection was found in 62 (31%) of 201 GBS patients and 12 (18%) of 65 FS patients. IgA anti-GMI antibody was detected in sera from 33 (16%) of the GBS patients, 1 (2%) of the FS patients, and none of the 46 normal control subjects. IgA anti-GM1 antibody titers were significantly higher in the GBS patients with positive C. jejuni serology than in those with negative serology (P < 0.0001) or the FS patients with positive C. jejuni serology (P = 0.007). IgA anti-GQ1b antibody was detected in sera from 18 (28%) of the FS patients, 9 (4%) of the GBS patients, and none of the normal control subjects. FS patients with positive C. jejuni serology had significantly higher titers of IgA anti-GQ1b antibody than those with negative serology (P = 0.01) or the GBS patients with positive C. jejuni serology (P < 0.0001). We conclude that anti-GM1 and anti-GQ1b IgA antibodies are closely associated with antecedent C. jejuni enteritis in GBS and FS, respectively.

Topics: Antibodies, Bacterial; Antibody Specificity; Autoantibodies; Autoimmune Diseases; Campylobacter Infections; Campylobacter jejuni; Enteritis; G(M1) Ganglioside; Gangliosides; Humans; Immunoglobulin A; Miller Fisher Syndrome; Nervous System Diseases; Polyradiculoneuropathy

Three Campylobacter jejuni, biotype 2, serotype O:41 strains that were isolated from patients who developed Guillain-Barré syndrome (GBS) and one C. jejuni isolate from a patient who developed enteritis only were examined. The aim of the study was to determine the structure of the core oligosaccharide (OS) of the lipopolysaccharide (LPS) of C. jejuni serotype O:41, a serotype rarely associated with the development of GBS, and to determine if the LPS shares similar epitopes with any of the major human gangliosides. Electrophoretic analysis with silver staining or immunoblotting demonstrated that the strains had LPS profiles characteristic of low-molecular-weight LPS. Colorimetric analysis detected N-acetylneuraminic (sialic) acid in the core OSs of all the strains. Thin-layer chromatography with immunostaining showed that antisera raised against the GBS strains reacted with the GM1 ganglioside, suggesting that C. jejuni serotype O:41 LPSs and the GM1 ganglioside have similar epitopes. Furthermore, polyclonal anti-GM1 and anti-asialoGM1 antibodies cross-reacted with each C. jejuni O:41 LPS tested, suggesting that the serotype O:41 core OS has a GM1- and asialoGM1-like structure. LPSs extracted from C. jejuni serostrains O:2, O:3, and O:19 were also used in the study. Cholera toxin (a GM1 ligand) and peanut agglutinin (a Galbeta1-3GalNAc ligand) recognized all serotype O:41 LPSs and the serostrain O:2 LPS. Immunoadsorption results confirmed GM1 relatedness. Moreover, the core OS was isolated from a GBS-associated C. jejuni O:41 LPS by gel permeation chromatography. An analysis by gas-liquid chromatography (GLC), GLC-mass spectrometry, and nuclear magnetic resonance showed the core OS of one of the C. jejuni O:41 GBS isolates to have a tetrasaccharide structure consistent with GM1 mimicry.

Topics: Adult; Animals; Antibodies; Campylobacter Infections; Campylobacter jejuni; Carbohydrate Sequence; Child; Cholera Toxin; Electrophoresis, Polyacrylamide Gel; Enteritis; Epitopes, B-Lymphocyte; Female; G(M1) Ganglioside; Humans; Infant; Lipopolysaccharides; Male; Molecular Sequence Data; N-Acetylneuraminic Acid; Peanut Agglutinin; Polyradiculoneuropathy; Rabbits

N-Acetylgalactosaminyl GD1a (GalNAc-GD1a) is a proposed target molecule for serum antibody in some patients with Guillain-Barré syndrome (GBS) (Kusunoki et al., 1994). We examined autoantibody to GalNAc-GD1a in sera from 58 GBS patients. Eight GBS patients had high IgG anti-GalNAc-GD1a antibody titers, 3 of whom also had high IgM anti-GalNAc-GD1a antibody titers. These 8 patients had experienced gastrointestinal infection before the onset of their neurological symptoms. Campylobacter jejuni was isolated from 4 of them. An absorption test indicated the presence of the GalNAc-GD1a epitope in lipopolysaccharides of C. jejuni. Sera that had anti-GalNAc-GD1a antibody reacted with several acidic glycolipids in bovine peripheral nerve, one of which was identified as N-acetylgalactosaminyl GM1b (GalNAc-GM1b). Serum binding to GalNAc-GM1b was decreased by absorption with GalNAc-GD1a. The presence of GalNAc-GM1b as well as GalNAc-GD1a has been reported in human peripheral nerves. We assume that C. jejuni, which bears the [GalNAc beta 1-4 (NeuAc alpha 2-3) Gal beta 1-3 GalNAc beta 1-] epitope, is the immunogen and that the glycoconjugates with the epitope are target molecules for the autoantibody in peripheral nerves of some GBS patients.

Topics: Animals; Antigens, Bacterial; Autoantibodies; Autoantigens; Campylobacter Infections; Cattle; Enteritis; G(M1) Ganglioside; Gangliosides; Glycolipids; Humans; Lipopolysaccharides; Polyradiculoneuropathy

Serum IgG anti-GM1 antibodies have been reported to occur in a variety of disorders, including Guillain-Barré syndrome and chronic polyneuropathies. Of over 5,000 serums tested in our laboratory, high titers of selective IgG anti-GM1 antibodies (> 1:1,000) and without binding to sulfatide were found in 35 patients. Clinical correlation revealed that almost all patients had axonal, motor neuropathies. One subgroup was comprised of individuals with an acute motor neuropathy, described either as an acute axonal Guillain-Barré-like syndrome that was occasionally associated with a prodrome of Campylobacter jejuni enteritis or as Chinese paralysis syndrome. A second group of patients had chronic asymmetric lower motor neuron (LMN) syndromes with no conduction block or other evidence of demyelination. The presence of selective high-titer IgG anti-GM1 antibody reactivity in serum is uncommon but when present is strongly associated with acute axonal motor neuropathies or chronic asymmetric LMN syndromes.

Topics: Antibodies; Axons; Campylobacter Infections; Demyelinating Diseases; Enteritis; G(M1) Ganglioside; Humans; Immunoglobulin G; Motor Neuron Disease; Paralysis; Polyradiculoneuropathy; Syndrome

We report a 4-year-old girl diagnosed as having Guillain-Barré syndrome after infection by Penner serotype 19 of Campylobacter jejuni. The patient had the HLA-B35 antigen. Neurological examination revealed distal-dominant weakness and intact sensation. Serial electrophysiological studies indicated that the predominant process was axonal degeneration involving motor nerves. An enzyme-linked immunosorbent assay revealed the presence of high titres of serum IgM antibodies to gangliosides GM1 and GM2. The IgM auto-antibody titres decreased concurrently with the clinical course of the illness and no switching from IgM to IgG secretion took place.

Topics: Antibodies, Anti-Idiotypic; Campylobacter Infections; Campylobacter jejuni; Child, Preschool; Electrophysiology; Enteritis; Female; G(M1) Ganglioside; Humans; Immunoglobulin M; Polyradiculoneuropathy

We report 2 patients with Guillain-Barré syndrome (GBS) following Campylobacter jejuni enteritis. Electrophysiologic studies indicated that the predominant process was axonal degeneration of motor nerves, and clinical recovery was poor. Serum testing by thin-layer chromatography and enzyme-linked immunosorbent assay revealed that the sera from both patients contained high titers of IgG antibody against GM1 ganglioside. These cases may represent a subgroup of GBS as acute axonal polyneuropathy following C jejuni enteritis associated with anti-GM1 antibodies.

Topics: Adult; Aged; Aged, 80 and over; Autoantibodies; Campylobacter Infections; Campylobacter jejuni; Enteritis; Female; G(M1) Ganglioside; Humans; Immunoglobulin G; Male; Motor Neurons; Neurons, Afferent; Polyradiculoneuropathy; Sural Nerve; Tibial Nerve; Ulnar Nerve