Antecedent infections in Fisher syndrome: a common pathogenesis of molecular mimicry.

Abstract

OBJECTIVE:

To assess the production mechanism of anti-GQ1b autoantibody in Fisher syndrome (FS).

METHODS:

The authors conducted a prospective case-control serologic study of five antecedent infections (Campylobacter jejuni, cytomegalovirus, Epstein-Barr virus, Mycoplasma pneumoniae, and Haemophilus influenzae) in 73 patients with FS and 73 sex- and age-matched hospital controls (HCs). Serologic evidence in FS patients of C. jejuni (21%) and H. influenzae (8%) infections was present significantly more often than in the HCs. None of the five pathogens examined was found in the 49 (67%) patients with FS. Anti-GQ1b IgG antibody was detected in most FS patients infected with C. jejuni or H. influenzae. Mass spectrometry analysis identified a C. jejuni strain (CF93-6) carrying a GT1a-like lipo-oligosaccharide (LOS) that had been isolated from an FS patient. Immunization of complex ganglioside-lacking knockout mice with the GT1a-like LOS generated IgG class monoclonal antibodies (mAbs) that reacted with GQ1b and GT1a. Thin-layer chromatography with immunostaining showed that anti-GQ1b mAb bound to the C. jejuni LOS (50% of the 20 FS-related strains) more commonly than in the Guillain-Barré syndrome (GBS)-related (7% of 70) or enteritis-related (20% of 65) strains. Anti-GM1 and anti-GD1a mAbs also reacted with the LOS from some FS-related strains (both 20%), but binding frequencies were higher in the GBS-related strains (74 and 57%). The GQ1b epitope was detected in 4 (40%) of the 10 FS-related H. influenzae strains but was absent in strains from patients with GBS (n = 4) and uncomplicated respiratory infections (n = 10).

CONCLUSIONS:

C. jejuni and H. influenzae are related to Fisher syndrome (FS) development, and production of anti-GQ1b autoantibody is mediated by the GQ1b-mimicking lipo-oligosaccharides on those bacteria. The causative agents remain unclear in the majority of patients with FS.

• Authors: M Koga, M Gilbert, J Li, S Koike, M Takahashi, K Furukawa, K Hirata, N Yuki
• Journal: Neurology (Neurology) Vol. 64 Issue 9 Pg. 1605-11 (May 10 2005) ISSN: 1526-632X [Electronic] United States
• PMID: 15883324 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Autoantibodies
• Gangliosides
• Lipopolysaccharides
• lipid-linked oligosaccharides
• GT1aalpha ganglioside
• GQ1b ganglioside

Topics

• Adult
• Animals
• Autoantibodies (blood, immunology)
• Campylobacter Infections (complications, immunology)
• Campylobacter jejuni (immunology)
• Case-Control Studies
• Cytomegalovirus Infections (complications, immunology)
• Epstein-Barr Virus Infections (complications, immunology)
• Female
• Gangliosides (immunology)
• Haemophilus Infections (complications, immunology)
• Haemophilus influenzae (immunology)
• Humans
• Lipopolysaccharides (immunology)
• Male
• Mice
• Mice, Knockout
• Middle Aged
• Miller Fisher Syndrome (blood, immunology, virology)
• Molecular Mimicry (immunology)
• Mycoplasma Infections (complications, immunology)
• Prospective Studies