重症肌无力自身抗体的特异性和序列分析

Specificity and Sequence Analysis of Autoantibodies in Myasthenia Gravis

通过对2株乙酰胆碱受体（AChR）自身抗体分子结构以及与致病性关系的分析，探讨了重症肌无力（MG）的发病机理。这2株抗体均为抗AChR上主要免疫原区（MIR）抗体，二者重链核苷酸同源性为99.7％，轻链同源性只有64.8％，说明重链在与AChRMIR结合上起重要作用。这2株抗体均未能在健康大鼠体内诱导出MG。通过与致病性AChR抗体可变区基因序列比较发现，这2株抗体的分子结构尤其是互补决定区（CDR）的氨基酸组成与致病性AChR抗体不同，表明抗AChRMIR抗体并不都具有致病性。

Objective To investigate the molecular structure of antibodies against acetylcholine receptor (AChR) in relation to their specificity. Methods To analyse the pathogenicity of the antibodies by passive transfer of them into rats, and the nucleotide and amino acid sequences of variable regions of the antibodies. Results Two antibodies studied shared the same heavy chains (99. 7% homology at nucleotide level), but used different light chains (64. 8% homology at nucleotide level), suggesting that heavy chain plays more important role in binding to AChR. Both antibodies were directied against main irnmunogenic regions (MIR) as showed by a competitive inhibition ELISA, but failed to induce experimental autoimmune myasthenia gravis (EAMG). The comparison of sequences of variable regions between the antibodies and a mouse pathogenic monoclonal antibody against AChR MIR shows that there is great difference in complernentarity determining regions (CDR) at hoth nucleotide and amino acid levels. Conclusion Not are all the antibodies against AChR MIR pathogehic and special molecular structure of pathogenic antibodies is needed in induction of MG and EAMG.