Experimental autoimmune MuSK antibody-induced myasthenia gravis

实验性自身免疫 MuSK 抗体诱导的重症肌无力

• 批准号: 17590883
• 负责人: MOTOMURA Masakatsu
• 金额: $ 2.24万
• 依托单位: Nagasaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590883/
• 关键词: myasthenia gravis; muscle-specific tyrosine kinase MuSK; AChR; autoantibody; target antigen; animal model; immunization; rat

Heading : The aim of this study is to investigate the pathogenesis and characteristics of muscle-specific tyrosine kinase (MuSK) antibody in experimental autoimmune myasthenia gravis (EAMG) rat.Background : Some of generalized seronegative MG patients have antibodies (Ab) against MuSK. But it is not clear how the Ab cause myasthenic symptoms. We investigated the pathogenesis of MuSK Ab using rat.Methods : Female Lewis rats, aged 8 weeks were inoculated twice in multiple intradermal sites, either MuSK protein (10-100μg) in complete Freund' s adjuvant (CFA) and Bordetella pertussis as co-adjuvant or the controls. Soluble mouse MuSK-6xHis protein was purified from HEK293.Results : Th3 weights of MuSK-immunized rats were lower than those of the control rats. The titers of antibodies to MuSK raised markedly compared with those of the controls. The electrophysiological examination using diaphragm was negative. The quantity of AChR and MuSK at the endplates of limb muscles were reduced in MuSK-immunized rats, compared with those of the control rats. The morphological changes, AChR-declustering muscle fibers have appeared in the MuSK-immunized rat (EDL, white muscle > soleus, red muscle).Conclusions : Our results suggest that anti-MuSK antibodies in MuSK-immunized rat may down-regulate MuSK and AChR, lead to the morphological changes in motor endplates. Further investigations will draw the conclusion whether MuSK Ab may be pathogenic or not.

标题：本研究旨在探讨实验性自身免疫性重症肌无力（EAMG）大鼠肌肉特异性酪氨酸激酶（MuSK）抗体的特点及发病机制。但目前尚不清楚抗体如何引起肌无力症状。方法：8周龄雌性刘易斯大鼠皮内接种MuSK抗体（10-100μg），并以百日咳杆菌为佐剂，免疫2次。从HEK 293中纯化小鼠可溶性MuSK-6xHis蛋白。结果：MuSK免疫组大鼠Th 3细胞数明显低于对照组。MuSK抗体滴度较对照组明显升高。膈肌电生理检查阴性。与对照组相比，MuSK免疫组大鼠肢体肌肉终板AChR和MuSK的数量减少。结论：抗MuSK抗体可下调MuSK免疫大鼠的MuSK和AChR，导致运动终板的形态学改变。MuSK抗体是否具有致病性有待进一步研究。

项目成果

重症筋無力症の病態、抗MuSK抗体の臨床的意義

重症肌无力的病理学及抗MuSK抗体的临床意义

• 发表时间: 2005
• 期刊: Clinical Neuroscience 23巻4号
• 作者: 本村政勝他;M.Motomura et al.;本村政勝他;白石裕一他;本村政勝他;鈴木秀和他;Nakano J et al.;本村政勝他
• 通讯作者: 本村政勝他

Infantile onset myasthenia gravis with MuSK antibodies.

具有 MuSK 抗体的婴儿型重症肌无力。

• 发表时间: 2006
• 期刊: Neurology 67
• 作者: Murai H;et al.
• 通讯作者: et al.

Dok-7 mutations underlie a neuromuscular junction synaptopathy

• DOI: 10.1126/science.1130837
• 发表时间: 2006-09-29
• 期刊: SCIENCE
• 影响因子: 56.9
• 作者: Beeson, David;Higuchi, Osamu;Yamanashi, Yuji
• 通讯作者: Yamanashi, Yuji

重症筋無力症の基礎知識、神経筋接合部の病態

重症肌无力基础知识、神经肌肉接头病理学

• 发表时间: 2005
• 期刊: Clinical Neuroscience 23巻4号
• 作者: 本村政勝他;M.Motomura et al.;本村政勝他;白石裕一他;本村政勝他;鈴木秀和他;Nakano J et al.;本村政勝他;辻畑光宏他
• 通讯作者: 辻畑光宏他

Acetylcholine receptors loss and postsynaptic damage in MuSK antibody-positive myasthenia gravis

• DOI: 10.1002/ana.20341
• 发表时间: 2005-02-01
• 期刊: ANNALS OF NEUROLOGY
• 影响因子: 11.2
• 作者: Shiraishi, H;Motomura, M;Eguchi, K
• 通讯作者: Eguchi, K