Experimental autoimmune MuSK antibody-induced myasthenia gravis

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）抗体的发病机制和特点。背景：部分MG全身性血清阴性患者存在针对麝香的抗体（Ab）。但目前尚不清楚Ab型血是如何引起肌无力症状的。我们用大鼠研究了麝香Ab的发病机制。方法：8周龄雌性Lewis大鼠多次皮内接种，麝香蛋白（10-100μg）作为完全弗氏佐剂（CFA），百日咳杆菌作为共佐剂或对照。可溶性小鼠麝香- 6xhis蛋白从HEK293中纯化。结果：麝香免疫大鼠Th3体重明显低于对照大鼠。与对照组相比，MuSK抗体的滴度显著提高。膈肌电生理检查为阴性。麝香免疫大鼠肢体肌肉终板AChR和麝香的数量较对照大鼠减少。麝香免疫大鼠（EDL，白色肌>比目鱼肌，红色肌）出现了形态学改变，achr散簇肌纤维。结论：麝香免疫大鼠的抗麝香抗体可能下调麝香和AChR，导致运动终板的形态学改变。进一步的调查将得出是否有致病的结论。

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.