Marchiori P E, Scaff M, Cossermelli W, De Assis J L
Arq Neuropsiquiatr. 1984 Dec;42(4):380-3. doi: 10.1590/s0004-282x1984000400010.
The development of autoimmune diseases in some patients treated with D-penicillamine (DPA) suggests that the reported occurrence of a conduction disorder at the neuromuscular junction and the development of a reversible myasthenia gravis in rheumatoid disease, progressive systemic sclerosis or Wilson's disease after the use of DPA are part of a general predisposition for autoimmune disease related to DPA therapy. The case reported is an example. The DPA- induced myasthenia gravis (MG) is similar to the spontaneous MG clinically and electrophysiologically, though ocular signs prevail in the former. Antibodies to acetylcholine receptor have been demonstrated and thymic hyperplasia also has been formed. Regarding the onset of myasthenic manifestations the duration of the treatment with DPA varies from 6 to 10 months. The action of DPA on the neuromuscular junction is different from that occurring in spontaneous MG. The pathogenesis of the DPA induced MG is still obscure. The chemical properties of DPA permit it to react with many proteins and some alteration of proteins may appear, with structural changes in the composition and antigenicity of the collagen fibers. In vitro DPA causes disorder of acetylcholine receptor bridges to alpha, beta, gamma sub-units with reduction of the S-S bridges in the gamma-subunit. This decreases the linkage of high affinity and abolishes its positive cooperative system, reducing the S-S connection in the alpha-unit near the acetylcholine linkage. The interaction between DPA and receptor may induce antigenic alteration in this latter, starting the autoimmune phenomena. The other possibility is the stimulation of prostaglandin E-1 synthesis by DPA may fill the allosteric place of ACh receptor, interfering on the neuromuscular junction.
一些接受青霉胺（DPA）治疗的患者出现自身免疫性疾病，这表明在类风湿性疾病、进行性系统性硬化症或威尔逊病患者使用DPA后，所报道的神经肌肉接头传导障碍以及可逆性重症肌无力的发生是与DPA治疗相关的自身免疫性疾病普遍易感性的一部分。所报道的病例就是一个例子。DPA诱发的重症肌无力（MG）在临床和电生理方面与自发性MG相似，尽管前者以眼部症状为主。已证实存在乙酰胆碱受体抗体，并且也已形成胸腺增生。关于肌无力表现的发作，DPA治疗的持续时间为6至10个月不等。DPA对神经肌肉接头的作用与自发性MG不同。DPA诱发MG的发病机制仍不清楚。DPA的化学性质使其能够与许多蛋白质发生反应，可能会出现一些蛋白质改变，胶原纤维的组成和抗原性会发生结构变化。在体外，DPA会导致乙酰胆碱受体与α、β、γ亚基的桥接紊乱，γ亚基中的二硫键减少。这会降低高亲和力的连接并消除其正协同系统，减少乙酰胆碱连接附近α亚基中的二硫键连接。DPA与受体之间的相互作用可能会在后者中诱导抗原性改变，从而引发自身免疫现象。另一种可能性是DPA刺激前列腺素E-1合成，可能占据乙酰胆碱受体的变构位点，干扰神经肌肉接头。
