| Project/Area Number |
15590895
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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 |
Neurology
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| Research Institution | Nagasaki University |
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Principal Investigator |
YOSHIMURA Toshiro Nagasaki University, School of Medicine, Professor, 医学部, 教授 (80182822)
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| Co-Investigator(Kenkyū-buntansha) |
OKITA Minoru Seijyo University, Department of Rehabiritation, Associate Professor, リハビリテーション部, 助教授 (50244091)
MOTOMURA Masakatsu Nagasaki University, Graduate School of Biomedical Sciences, Lecturer, 大学院・医歯薬学総合研究科, 講師 (70244093)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2005: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2003: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | Anti-MuSK antibody / anti-AChR Ab / seronegative / Myasthenia gravis / motor end- plate / fine structure / MuSK / acetylcholine receptor / アセチルコリンレセプター / seronegative MG / 補体 / TypeI線維 / 形態 / sero-negative MG / 血清抗アセチルコリン受容体抗体 |
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| Research Abstract |
Myasthenia gravis(MG) is an antibody-mediated autoimmune disease of the neuromuscular junction. In approximately 80% of patients, auto-antibodies are classified as seronegative. In 2001, Hoch et al, first showed that 70% of AChR-Ab-seronegative MG patients, but not AChR-Ab-seropositive MG patients, have serum auto-antibodies against the muscle-specific tyrosin kinase(MuSK), which mediates agrin-induced clustering of AchRs during synaps formation, and is also expressed at the mature neuromuscular junction. Subsequent studies of AChR-Ab-seronegative MG patients reported seropositivity from 3.8% to 71% and that AChR-Ab-seronegative MG patients had antibodies to a 110kDa protein, identified as MuSK. Clinical aspects of the MuSK Ab-positive MG are the following ; 1)female-dominant, with onset between ages 20 to 60 years, 2)patients had prominent neck or respiratoru muscle weakness, 3)response to cholinesterase inhibitors was variable, 4)all patients with ocular type MG are negative for MuSK antibodies, 5)absence of thymoma, and no improvement after thymectomy. 6)most patients had a good response to plasma exchange and steroid therapy, but a proportion of MuSK Ab positive MG patients who present muscle atrophy had a poor prognosis. Pathological study of motor end-plate from the MuSK Ab- positive MG show the following results ; all of the MuSK Ab- positive MG patient showed typeII fiber atrophy but there are no myopathic changes. The postsynaptic area become small and preserved of postsynaptic density. MuSK antibody status should help diagnose MG with atypical presentations and ensure appropriate patient treatment. Furtherexaminations to elucidate the pathomechanism of MuSK antibodies are needed.
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