Richman D P, Agius M A
Department of Neurology, University of California, Davis.
Neurol Clin. 1994 May;12(2):273-84.
Much of the remarkable advance in our understanding of the immunopathology of MG relates to the availability of two gifts of nature that permit the ready purification of the antigen, AChR. Immunization of experimental animals with AChR has led to the development of the extremely faithful animal model, EAMG. Analysis of both EAMG and MG has revealed that the effector agents in this autoimmune disease are anti-AChR antibodies, whose production is regulated by anti-AChR CD4+ T cells. The pathogenic effects on neuromuscular transmission are mediated by antibody-induced antigenic modulation of end-plate AChR, end-plate membrane destruction through complement fixation and recruitment of inflammatory cells, and antibody-induced blockade of the function of the remaining AChR molecules. The origin of MG remains unknown. One theory proposes that dysregulation of the thymic control of tolerance plays an important role. An alternative hypothesis is that tolerance is broken as the result of a vigorous immune response directed against an invading microorganism that expresses a molecule that is similar to AChR, so-called molecular mimicry. This "normal" response eventually cross-reacts with self-AChR, resulting in the autoimmune damage. Our current knowledge of MG has suggested a number of possible sites of therapeutic intervention that are under active study. Future information concerning the origin of the disease will likely be useful in the design of more effective treatment for this and other related autoimmune diseases.
我们对重症肌无力（MG）免疫病理学认识的显著进展，在很大程度上得益于大自然赋予的两份礼物，它们使得抗原乙酰胆碱受体（AChR）能够轻易地被纯化。用AChR对实验动物进行免疫，导致了极为逼真的动物模型——实验性自身免疫性重症肌无力（EAMG）的建立。对EAMG和MG的分析均显示，这种自身免疫性疾病中的效应因子是抗AChR抗体，其产生受抗AChR CD4 + T细胞调节。对神经肌肉传递的致病作用是由抗体诱导的终板AChR抗原调制、通过补体固定和炎症细胞募集导致的终板膜破坏，以及抗体诱导的剩余AChR分子功能阻断介导的。MG的病因仍然不明。一种理论认为，胸腺对耐受性的控制失调起重要作用。另一种假说是，针对表达与AChR相似分子的入侵微生物的强烈免疫反应导致耐受性被打破，即所谓的分子模拟。这种“正常”反应最终与自身AChR发生交叉反应，导致自身免疫性损伤。我们目前对MG的了解提示了一些正在积极研究的可能治疗干预位点。关于该疾病病因的未来信息可能有助于设计针对这种及其他相关自身免疫性疾病的更有效治疗方法。
