| Project/Area Number |
14370210
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Dokkyo University School of Medicine |
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Principal Investigator |
YUKI Nobuhiro Dokkyo University School of Medicine, Department of Neurology, Associated Professor, 医学部, 助教授 (60285913)
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| Co-Investigator(Kenkyū-buntansha) |
YAMADA Mitsunori Niigata University, Department of Pathology, Brain Research Institute, Associated Professor, 脳研究所, 助教授 (30240039)
UEDA Syuichi Dokkyo University School of Medicine, Department of Neurology, Professor, 医学部, 教授 (60150570)
KOBATA Tetsuji Dokkyo University School of Medicine, Department of Neurology, Professor, 医学部, 教授 (10205445)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥10,400,000 (Direct Cost: ¥10,400,000)
Fiscal Year 2003: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥6,800,000 (Direct Cost: ¥6,800,000)
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| Keywords | Guillain-Barre syndrome / molecular mimicry / lipo-oligosaccharide / animal model / autoimmune disease / フィッシャー症候群 / Haemophilus influenzae / 症例対照試験 / Campylobacter jejuni / リポ多糖 / 疾患モデル |
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| Research Abstract |
Molecular mimicry between microbial and self components is postulated as the mechanism that accounts for the antigen and tissue specificity of immune responses in post-infectious autoimmune diseases. Little direct evidence exists, and research in this area has focused principally on T cell-mediated, anti-peptide responses, rather than on humoral responses to carbohydrate structures. Guillain-Barre syndrome, the most frequent cause of acute neuromuscular paralysis, occurs 1 to 2 weeks after various bacterial and viral infections, particularly Campylobacter jejuni enteritis. Carbohydrate mimicry between the bacterial lipo-oligosaccharide and human GM1 ganglioside is seen as having relevance to the pathogenesis of Guillain-Barre syndrome, and conclusive evidence is reported here. On sensitization with C.jejuni lipo-oligosaccharide, rabbits developed anti-GM1 IgG antibody and flaccid limb weakness. Paralyzed rabbits had pathological changes in their peripheral nerves identical to those present in Guillain-Barre syndrome. Immunization of mice with the lipo-oligosaccharide generated a monoclonal antibody that reacted with GM1 and bound to human peripheral nerves. The monoclonal antibody and anti-GM1 IgG from patients with Guillain-Barre syndrome blocked muscle action potentials in a muscle-spinal cord co-culture, indicative that anti-GM1 antibody can cause muscle weakness. These findings show that carbohydrate mimicry is an important cause of autoimmune neuropathy.
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