Antecedent infections in Fisher syndrome: a common pathogenesis of molecular mimicry.
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.
Koga
M
M
Department of Neurology, Dokkyo University School of Medicine, Shimotsuga, Tochigi, Japan. kogamrk@dokkyomed.ac.jp
Gilbert
M
M
Li
J
J
Koike
S
S
Takahashi
M
M
Furukawa
K
K
Hirata
K
K
Yuki
N
N
D000328:Adult; D000818:Animals; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D002169:Campylobacter Infections / Q000150:complications* / Q000276:immunology; D016123:Campylobacter jejuni / Q000276:immunology; D016022:Case-Control Studies; D003586:Cytomegalovirus Infections / Q000150:complications / Q000276:immunology; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000276:immunology; D005260:Female; D005732:Gangliosides / Q000276:immunology*; D006192:Haemophilus Infections / Q000150:complications* / Q000276:immunology; D006193:Haemophilus influenzae / Q000276:immunology; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D019846:Miller Fisher Syndrome / Q000097:blood / Q000276:immunology* / Q000821:virology; D018716:Molecular Mimicry / Q000276:immunology*; D009175:Mycoplasma Infections / Q000150:complications / Q000276:immunology; D011446:Prospective Studies
D001323:Autoantibodies; D005732:Gangliosides; D008070:Lipopolysaccharides; C023023:lipid-linked oligosaccharides; C084318:GT1aalpha ganglioside; C039129:GQ1b ganglioside