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From the Departments of Neurology (Drs. Koga, Hirata, and Yuki) and Microbiology (Dr. Masuda), Dokkyo University School of Medicine, Tochigi; and Department of Microbiology (Dr. Takahashi), Tokyo Metropolitan Institute of Public Health, Japan.
Address correspondence and reprint requests to Dr. M. Koga, Department of Neurology, Dokkyo University School of Medicine, Kitakobayashi 880, Mibu, Shimotsuga, Tochigi 321-0293, Japan; e-mail: kogamrk{at}dokkyomed.ac.jp
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.
Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of Contents for the November 8 issue to find the title link for this article.
Editorial, see page 1350
This article was previously published in electronic format as an Expedited E-Pub on September 14, 2005, at www.neurology.org.
Supported in part by grants from the Ichiro Kanehara Foundation to M.K.; the Kanae Foundation for Life & Socio-Medical Science to M.K.; the Japan Intractable Diseases Research Foundation to M.K.; Mizutani Foundation for Glycoscience to N.Y.; a grant for Scientific Research (B) (KAKENHI 14370210 to N.Y.) from the Ministry of Education, Culture, Sports, Science and Technology of Japan; a Research Grant for Neuroimmunological Diseases to N.Y. from the Ministry of Health, Labour and Welfare of Japan; a Health Sciences Research Grant (Research on Psychiatric and Neurological Diseases and Mental Health) to N.Y. from the Ministry of Health, Labour, and Welfare of Japan; and a grant from the Human Frontier Science Program (RGP0038/2003-C to N.Y.).
Disclosure: The authors report no conflicts of interest.
Received April 4, 2005. Accepted in final form June 20, 2005.
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