Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, Netherlands; School of Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, Netherlands.
argenx, Zwijnaarde, Belgium, University of California, Irvine, CA, USA.
Autoimmun Rev. 2022 Jul;21(7):103104. doi: 10.1016/j.autrev.2022.103104. Epub 2022 Apr 19.
The presence of autoantibodies directed against the muscle nicotinic acetylcholine receptor (AChR) is the most common cause of myasthenia gravis (MG). These antibodies damage the postsynaptic membrane of the neuromuscular junction and cause muscle weakness by depleting AChRs and thus impairing synaptic transmission. As one of the best-characterized antibody-mediated autoimmune diseases, AChR-MG has often served as a reference model for other autoimmune disorders. Classical pharmacological treatments, including broad-spectrum immunosuppressive drugs, are effective in many patients. However, complete remission cannot be achieved in all patients, and 10% of patients do not respond to currently used therapies. This may be attributed to production of autoantibodies by long-lived plasma cells which are resistant to conventional immunosuppressive drugs. Hence, novel therapies specifically targeting plasma cells might be a suitable therapeutic approach for selected patients. Additionally, in order to reduce side effects of broad-spectrum immunosuppression, targeted immunotherapies and symptomatic treatments will be required. This review presents established therapies as well as novel therapeutic approaches for MG and related conditions, with a focus on AChR-MG.
针对肌肉烟碱型乙酰胆碱受体（AChR）的自身抗体的存在是重症肌无力（MG）最常见的原因。这些抗体通过耗尽 AChR 从而损害突触传递来破坏神经肌肉接头的突触后膜，导致肌肉无力。作为研究最透彻的抗体介导的自身免疫疾病之一，AChR-MG 通常被用作其他自身免疫疾病的参考模型。包括广谱免疫抑制剂在内的经典药理学治疗方法对许多患者有效。然而，并非所有患者都能完全缓解，且 10%的患者对目前使用的疗法无反应。这可能归因于对常规免疫抑制剂有抗性的长寿浆细胞产生的自身抗体。因此，针对浆细胞的新型治疗方法可能是某些患者的合适治疗方法。此外，为了减少广谱免疫抑制的副作用，还需要靶向免疫疗法和对症治疗。本文重点介绍了针对 AChR-MG 的已确立疗法以及针对 MG 和相关疾病的新型治疗方法。
