PATHOGENICITY AND SEQUENCE ANALYSIS OF A MOUSE MONOCLONAL ANTIBODY AGAINST HUMAN ACETYLCHOLINE RECEPTOR IN MYASTHENIA GRAVIS

通过对乙酰胆碱受体（ＡＣｈＲ）自身抗体分子结构以及与致病性关系的研究探讨重症肌无力（ＭＧ）及其动物模型——实验性自身免疫性重症肌无力（ＥＡＭＧ）的发病机理。ＡＣｈＲ抗体被动转移至大鼠后诱导出明显的ＥＡＭＧ。全身肌肉ＡＣｈＲ损失率和体重减轻率达４７．２±１５．３％和１３．４±２．２％。这株ＡＣｈＲ抗体的重链可变区基因由小鼠Ｑ５２胚系基因编码，其同源性为９４．８％，将这株抗体的重链和轻链可变区、尤其是互补决定区（ＣＤＲ）的核苷酸和氨基酸序列与其他致病性ＡＣｈＲ抗体比较发现，能诱导ＭＧ和ＥＡＭＧ的致病性ＡＣｈＲ抗体的结构并不是完全一致的。

PATHOGENICITY AND SEQUENCE ANALYSIS OF A MOUSE MONOCLONAL ANTIBODY AGAINST HUMAN ACETYLCHOLINE RECEPTOR IN MYASTHENIA GRAVIS

The pathogenesis of myasthenia gravis(MG) on the animal model of experimental autoimmune myasthenia gravis (EAME) was investigated. The pathogenicity of a mouse monoclonal antibody against human acetylcholine receptor (AChR) was determined on the rats and the sequences of the variable regions of the antibody analysed. The anti-AChR antibody studied could induce EAMG. AChR and weight loss by 47.2 + 15.3 % and 13.4±2.2% respectively after passively transferred into rats. The heavy chain genetic element of the antibody, which showed a 94.8% homology with the most closely related germline VH, was derived from the Q52 germline family.Comparison of the variable region sequences, especially the complementarity determining regions (CDRs) with the antibody and other pathogenic anti-AChR antibodies indicates that not is the unique structure of pathogenic antiAChR antibodies needed in mediating MG and EAMG.