2010 Fiscal Year Final Research Report
New model of molecular mimicry by bacterial molecule complex formation
| Project/Area Number |
20590446
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Bacteriology (including Mycology)
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| Research Institution | Yamaguchi University |
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Principal Investigator |
KOGA Michiaki Yamaguchi University, 医学部附属病院, 講師 (60383014)
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| Project Period (FY) |
2008 – 2010
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| Keywords | 分子相同性 / ガングリオシド / カンピロバクター / ギラン・バレー症候群 |
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| Research Abstract |
Campylobacter jejuni is a leading cause of Guillain-Barre syndrome (GBS), a postinfectious autoimmune polyneuropathy. We assumed that complex formation of GM1- and GD1a-like lipo-oligosaccharides (LOSs) on the bacteria makes the organisms express new structure, as a result generating autoantibody which has different reactivity from antibodies specific for each ganglioside. Autoantibody against mixture of GM1 and GD1a (cM1/D1a) was detected in 14 (25%) of 57 GBS patients from whom C. jejuni strains carrying both GM1- and GD1a-like LOSs had been isolated, being more frequent than those whose isolates carrying only GM1 (1/11, 9.1%) or neither epitopes (5/51, 9.8%). All of these patients had higher titer of anti-GM1b IgG antibody, and absorption study showed that anti-GM1b and anti-cM1/Da antibodies were absorbed by GM1/GD1a-like LOS. Furthermore, these absorptions were lost when we used LOS as absorber after treatment with neuraminidase from Arthrobacter ureafaciens, which converts GM1/GD1a-like structure to GM1-like one. These findings strongly suggest that target structure for anti-cM1/D1a antibody mimics GM1b ganglioside, which has structurally different sugar sequence from GM1 and GD1a, but could also be directed for as target antigen for autoantibody in GBS. This is the first example demonstrating that complex formation of bacterial structures is another way to make molecular mimicry in autoantibody production.
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