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

基本信息

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

项目摘要

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：这项研究的目的是研究实验性自身免疫性肌无力肌无力重症（EAMG）大鼠的肌肉特异性酪氨酸激酶（MUSK）抗体的发病机理和特征：background。但是目前尚不清楚AB是如何引起肌无力症状的。我们使用大鼠研究了Musk AB的发病机理。方法：雌性刘易斯大鼠，在多个皮内部位接种了两次，在完整的弗雷德调整（CFA）中，麝香蛋白（10-100μg）在多个皮内部位接种了两次，将其作为共同添加剂或对照组进行。可溶性小鼠麝香-6xhis蛋白从HEK293中纯化：麝香免疫大鼠的Th3重量低于对照大鼠的Th3重量。与对照组相比，对麝香的抗体的滴度显着升高。使用隔膜的电生理检查为阴性。与对照大鼠相比，在麝香免疫的大鼠中，肢体肌肉终板处的ACHR和麝香的数量减少了。麝香免疫的大鼠（EDL，白色肌肉> soleus，红色肌肉）出现了形态变化，凝集的肌肉纤维。结论：我们的结果表明，在麝香免疫的大鼠中，抗肌肉抗体可能会下调麝香和ACHR，可能会导致运动终止底层中的形成终止。进一步的研究将得出结论，无论Musk AB是否可能是致病性的。