Kaplan I, Blakely B T, Pavlath G K, Travis M, Blau H M
Department of Pharmacology, Stanford University School of Medicine, CA 94305-5332.
Proc Natl Acad Sci U S A. 1990 Oct;87(20):8100-4. doi: 10.1073/pnas.87.20.8100.
Antibodies to the acetylcholine receptor (AChR), which are diagnostic of the human autoimmune disease myasthenia gravis, block AChR function and increase the rate of AChR degradation leading to impaired neuromuscular transmission. Steroids are frequently used to alleviate symptoms of muscle fatigue and weakness in patients with myasthenia gravis because of their well-documented immunosuppressive effects. We show here that the steroid dexamethasone significantly increases total surface AChRs on cultured human muscle exposed to myasthenia gravis sera. Our results suggest that the clinical improvement observed in myasthenic patients treated with steroids is due not only to an effect on the immune system but also to a direct effect on muscle. We propose that the identification and development of pharmacologic agents that augment receptors and other proteins that are reduced by human genetic or autoimmune disease will have broad therapeutic applications.
抗乙酰胆碱受体（AChR）抗体可诊断人类自身免疫性疾病重症肌无力，它会阻断AChR功能并加快AChR降解速度，导致神经肌肉传递受损。由于类固醇具有充分记录的免疫抑制作用，因此常用于缓解重症肌无力患者的肌肉疲劳和无力症状。我们在此表明，类固醇地塞米松可显著增加暴露于重症肌无力血清的培养人肌肉上的总表面AChR。我们的结果表明，接受类固醇治疗的重症肌无力患者所观察到的临床改善不仅归因于对免疫系统的作用，还归因于对肌肉的直接作用。我们提出，鉴定和开发可增加因人类遗传或自身免疫性疾病而减少的受体和其他蛋白质的药物制剂将具有广泛的治疗应用。
