Experimental autoimmune MuSK antibody-induced myasthenia gravis

目的：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)抗体的发病机制及特点。背景：部分泛发性血清阴性MG患者存在Musk抗体。但目前尚不清楚抗体是如何导致肌无力症状的。方法：8周龄雌性Lewis大鼠皮内接种麝香蛋白(10-100μg)和百日咳杆菌作为佐剂，对照组接种百日咳杆菌。从HEK293中纯化了小鼠可溶性麝香-6xHis蛋白。结果：免疫麝香的大鼠Th3重量低于对照组。与对照组相比，马斯克抗体效价显著升高。采用隔膜的电生理检查均为阴性。与对照组相比，麝香免疫组大鼠肢体肌肉终板AChR和麝香的数量减少。麝香免疫大鼠(EDL、白肌、比目鱼肌、红肌)出现了形态改变，AChR-去聚肌纤维。结论：抗麝香抗体可下调麝香和AChR的表达，导致运动终板的形态改变。进一步的调查将得出结论，麝香抗体是否可能是致病的。

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.