Mihovilovic M, Donnelly-Roberts D, Richman D P, Martinez-Carrion M
Department of Medicine, Duke University, Durham, NC 27710.
J Immunol. 1994 Jun 15;152(12):5997-6002.
Three mAbs, mAbs 249E, 370, and 383C, directed against the alpha-bungarotoxin (alpha BgTx) binding site of the acetylcholine receptor (AChR) induce a hyperacute form of experimental autoimmune myasthenia gravis (EAMG), characterized by death within hours of mAb injection. To analyze the mechanisms of this effect, purified AChR-mAb complexes were investigated for their ability to bind the cholinergic agonist carbamoylcholine and to undergo agonist-induced activation of the cholinergic ionophore. The three mAbs inhibited carbamylcholine binding, and, conversely, their binding to AChR was inhibited by carbamylcholine. All three completely inhibited carbamylcholine-induced T1+ influxes to AChR-rich vesicles. These data indicate that the severe hyperacute EAMG induced by these mAbs results from blockage of AChR function and that the role of such potent Abs (even if present in small amounts) in the pathogenesis of human myasthenia gravis deserves further investigation.
三种单克隆抗体，即单克隆抗体249E、370和383C，它们靶向乙酰胆碱受体（AChR）的α-银环蛇毒素（αBgTx）结合位点，可诱发一种超急性形式的实验性自身免疫性重症肌无力（EAMG），其特征是在注射单克隆抗体数小时内死亡。为了分析这种效应的机制，对纯化的AChR-单克隆抗体复合物结合胆碱能激动剂氨甲酰胆碱的能力以及接受激动剂诱导的胆碱能离子载体激活的能力进行了研究。这三种单克隆抗体抑制氨甲酰胆碱的结合，相反，氨甲酰胆碱也抑制它们与AChR的结合。这三种单克隆抗体均完全抑制氨甲酰胆碱诱导的T1 +流入富含AChR的囊泡。这些数据表明，这些单克隆抗体诱发的严重超急性EAMG是由AChR功能受阻所致，而且这类强效抗体（即使含量很少）在人类重症肌无力发病机制中的作用值得进一步研究。
