| Project/Area Number |
23591248
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Nagasaki Institute of Applied Science (2013)
Nagasaki University (2011-2012) |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
FUKUDA Taku 長崎大学, 大学病院, 研究員 (50437894)
YOSHIMURA Toshiro 長崎大学, 大学院医歯薬学総合研究科, 教授 (80182822)
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2011: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
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| Keywords | 重症筋無力症 / 自己抗体 / 神経筋接合部疾患 / 新規自己抗体 / Lrp4 / LDL受容体関連蛋白質４ / アセチルコリン受容体 / 筋特異的受容体型チロシンキナーゼ |
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| Research Abstract |
Myasthenia gravis (MG) is caused by the failure of neuromuscular transmission mediated by pathogenic autoantibodies (Abs) against acetylcholine receptor (AChR) and muscle-specific receptor tyrosine kinase (MuSK). The seropositivity rates for routine AChR binding Ab and MuSK Ab in MG are 80-85% and 5-10% for MG patients in Japan, respectively. In 2011, autoantibodies against low-density lipoprotein receptor-related protein 4 (Lrp4) were identified in Japanese MG patients. We developed a simple technique termed Gaussia luciferase immunoprecipitation for detecting antibodies to Lrp4. As a result, nine generalized MG patients from 300 lacking AChR Ab are positive for Lrp4 antibodies. These antibodies inhibit binding of Lrp4 to its ligand and are predominantly of the IgG1 subclass. Further studies including neuromuscular junction biopsy are needed to clarify the pathomechanism of Lrp4 ab positive MG. These results indicate that Lrp4 is a third pathogenic autoantigen in patients with MG.
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