Engel A G
Ann Neurol. 1984 Nov;16(5):519-34. doi: 10.1002/ana.410160502.
More than a decade ago myasthenic symptoms were observed in rabbits immunized with acetylcholine receptor (AChR) [119] and AChR deficiency was found at the neuromuscular junction in human myasthenia gravis (MG) [36]. By 1977 the autoimmune character of MG and the pathogenic role of AChR antibodies had been established by several measures. These included the demonstration of circulating AChR antibodies in nearly 90% of patients with MG [87], passive transfer with IgG of several features of the disease from human to mouse [149], localization of immune complexes (IgG and complement) on the postsynaptic membrane [30], and the beneficial effects of plasmapheresis [20, 123]. Substantial subsequent progress has occurred in understanding the structure and function of AChR and its interaction with AChR antibodies. The relationships of the concentration, specificities, and functional properties of the antibodies to the clinical state in MG have been carefully analyzed, and the mechanisms by which AChR antibodies impair neuromuscular transmission have been further investigated. The clinical classification of MG has been refined, the role of the thymus gland in the disease has been further clarified, and new information has become available on transient neonatal MG. The prognosis for generalized MG is improving, but there is still no consensus on its optimal management. Novel therapeutic approaches to MG are now being explored in animal models. Recognition of the autoimmune origin of acquired MG also implied that myasthenic disorders occurring in a genetic or congenital setting had a different cause. As a result, a number of congenital myasthenic syndromes have come to be recognized and investigated. Finally, an acquired disorder of neuromuscular transmission different from MG, the Lambert-Eaton myasthenic syndrome, has also been shown to have an autoimmune basis. In this syndrome, active zone particles of the presynaptic membrane are direct or indirect targets of the pathogenic autoantibodies.
十多年前，在用乙酰胆碱受体（AChR）免疫的兔子中观察到肌无力症状[119]，并且在人类重症肌无力（MG）的神经肌肉接头处发现了AChR缺乏[36]。到1977年，通过多种方法确立了MG的自身免疫特性以及AChR抗体的致病作用。这些方法包括在近90%的MG患者中检测到循环AChR抗体[87]，用人IgG将该疾病的多个特征从人被动转移到小鼠[149]，免疫复合物（IgG和补体）在突触后膜上的定位[30]，以及血浆置换的有益效果[20, 123]。随后在理解AChR的结构和功能及其与AChR抗体的相互作用方面取得了实质性进展。已经仔细分析了抗体的浓度、特异性和功能特性与MG临床状态的关系，并进一步研究了AChR抗体损害神经肌肉传递的机制。MG的临床分类得到了完善，胸腺在该疾病中的作用得到了进一步阐明，并且关于短暂性新生儿MG也有了新的信息。全身型MG的预后正在改善，但在其最佳治疗方面仍未达成共识。目前正在动物模型中探索MG的新型治疗方法。认识到获得性MG的自身免疫起源也意味着在遗传或先天性背景下发生的肌无力疾病有不同的病因。因此，一些先天性肌无力综合征已得到认识和研究。最后，一种不同于MG的获得性神经肌肉传递障碍——兰伯特 - 伊顿肌无力综合征，也已被证明有自身免疫基础。在该综合征中，突触前膜的活性区颗粒是致病性自身抗体的直接或间接靶点。
