AChR单抗(A7)诱导大鼠了实验性重症肌无力的分子基础

Pathogenicity and sequence analysis of a mouse anti-AChR monoclonal antibody A7

乙酰胆碱受体（ＡＣｈＲ）抗体在重症肌无力（ＭＧ）和实验性自身免疫性重症肌无力（ＥＡＭＧ）患者体内可诱导ＡＣｈＲ丢失和肌力减退。通过对小鼠抗电鳐电器官的ＡＣｈＲ单抗Ａ７的致病性测定和可变区基因克隆与序列分析， 探讨致病性抗体介导的ＭＧ和ＥＡＭＧ的发病机制。Ａ７被动注射大鼠后可诱导出严重的ＥＡＭＧ，ＡＣｈＲ损失串达３８．４％±７．２％。Ａ７的Ｈ链Ｖ区由小鼠ＰＣ７１８３胚系基因编码与Ｄ和ＪＨ４连接，与ＤＦＬ１６．２胚系Ｖ_Ｈ基因具有９３．７％的同源性。Ｌ链Ｖ区由小鼠Ｖ_Ｋ３组基因编码，与Ｊｋ２连接，与Ｖｋ２１Ｅ胚系基因具有９８．１％的同源性。

Autoantibodies against the acetylcoline receptor ( AChR ) induce AChR loss and muscular weakness in myasthenia gravis(MG ) and experimental autoimmune myasthenia gravis( EAMG ) . The pathogenicity and sequences of variable regions of a mouse monoclonal antibody A7 directed against Torpedo AChR were investigated in this family. A7 passively transfered into rats was able to induce severe muscular weakness and AChR loss by 38. 4%±7. 2%. The heavy chain genetic elements of A7 ,which showed a 93. 7% homology with most closely related DEL 16. 2 germline V_H , was derived from mouse PC 7183 germline family A7 light chain V region , the identity of which was 98. 1% as compared with Vk 2 1E germline gene , was encoded by mouse Vk3 subgroup gene.