Project/Area Number |
16390254
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Neurology
|
Research Institution | Dokkyo Medical University |
Principal Investigator |
YUKI Nobuhiro Dokkyo Medical University School, Department of Neurology, Associate Professor, 医学部, 助教授 (60285913)
|
Co-Investigator(Kenkyū-buntansha) |
MASUDA Michiaki Dokkyo Medical University School, Department of Neurology, Professor, 医学部, 教授 (80199702)
小島 直也 東海大学, 工学部, 助教授 (30183338)
|
Project Period (FY) |
2004 – 2005
|
Project Status |
Completed (Fiscal Year 2005)
|
Budget Amount *help |
¥10,400,000 (Direct Cost: ¥10,400,000)
Fiscal Year 2005: ¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 2004: ¥6,200,000 (Direct Cost: ¥6,200,000)
|
Keywords | Guillain-Barre syndrome / Campylobacter jejuni / Lipo-oligosaccharide / Molecular mimicry / 遺伝子多型 / ガングリオシド |
Research Abstract |
Guillain-Barre syndrome (GBS), a post-infectious autoimmune-mediated neuropathy, is a serious complication after Campylobacter jejuni enteritis. To investigate the bacterial risk factor for developing GBS, genotypes, serotypes and ganglioside-mimics on lipo-oligosaccharide (LOS) were analyzed in the isolates from Japanese patients. GBS isolates more frequently were grouped in LOS biosynthesis locus class A (72/106 ; 68%) than were enteritis isolates (17/103 ; 17%). Class A strains predominantly had genotype cst-II (Thr51), which is responsible for biosynthesis of GM1- and GD1a-like LOSs. Indeed we found that strains with cst-II (Thr51) regularly expressed the GM1 and GD1a epitopes, whereas those with cst-II (Asn51) had the GQ1b epitope. Patients who had C.jejuni (Thr51) more frequently were positive for anti-GM1 and anti-GD1a IgG and had limb weakness. Patients infected with C.jejuni (Asn51) more often were positive for anti-GQ1b IgG and had ophthalmoparesis and ataxia. Predominant cst-II genotype was Thr51 in the isolates from GBS patients, whereas it was Asn51 in those with Fisher syndrome. Class A locus clustering in GBS isolates, recently reported in Europe, provides the first GBS-related C.jejuni characteristic common to Asia and Europe. Class A locus seems to be linked to cst-II polymorphism, resulting in promotion of both GM1- and GD1a-like structure synthesis on LOS ; consequently, increasing the risk of producing anti-ganglioside antibodies and developing GBS. The genetic polymorphism of C.jejuni determines autoantibody reactivity and the clinical presentation of GBS, possibly through modification of the host-mimicking molecule.
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