Campylobacter gene polymorphism as a determinant of clinical features of Guillain-Barré syndrome.
BACKGROUND
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.


OBJECTIVE
To examine the hypothesis that this polymorphism determines autoantibody reactivity, and thereby neurologic presentations in GBS.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Koga
M
M
Department of Neurology, Dokkyo University School of Medicine, Kitakobayashi 880, Mibu, Shimotsuga, Tochigi 321-0293, Japan. kogamrk@dokkyomed.ac.jp
Takahashi
M
M
Masuda
M
M
Hirata
K
K
Yuki
N
N
D001323:Autoantibodies / Q000276:immunology; D002169:Campylobacter Infections / Q000150:complications / Q000276:immunology*; D016123:Campylobacter jejuni / Q000235:genetics* / Q000276:immunology*; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D005677:G(M1) Ganglioside / Q000276:immunology; D005732:Gangliosides / Q000276:immunology; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics; D020275:Guillain-Barre Syndrome / Q000276:immunology* / Q000382:microbiology; D006801:Humans; D008070:Lipopolysaccharides / Q000096:biosynthesis / Q000276:immunology*; D018716:Molecular Mimicry / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics; D013045:Species Specificity
D001323:Autoantibodies; D000939:Epitopes; D005732:Gangliosides; D008070:Lipopolysaccharides; C023023:lipid-linked oligosaccharides; D005677:G(M1) Ganglioside; C039129:GQ1b ganglioside