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Abstract：
Myasthenia Gravis (MG) is a chronic disabling autoimmune disease caused by autoantibodies to the neuromuscular junction (NMJ), characterized clinically by fluctuating weakness and early fatigability of ocular, skeletal and bulbar muscles. Despite being commonly considered a prototypic autoimmune disorder, MG is a complex and heterogeneous condition, presenting with variable clinical phenotypes, likely due to distinct pathophysiological settings related with different immunoreactivities, symptoms\' distribution, disease severity, age at onset, thymic histopathology and response to therapies. Current treatment of MG based on international consensus guidelines allows to effectively control symptoms, but most patients do not reach complete stable remission and require life-long immunosuppressive (IS) therapies. Moreover, a proportion of them is refractory to conventional IS treatment, highlighting the need for more specific and tailored strategies. Precision medicine is a new frontier of medicine that promises to greatly increase therapeutic success in several diseases, including autoimmune conditions. In MG, B cell activation, antibody recycling and NMJ damage by the complement system are crucial mechanisms, and their targeting by innovative biological drugs has been proven to be effective and safe in clinical trials. The switch from conventional IS to novel precision medicine approaches based on these drugs could prospectively and significantly improve MG care. In this review, we provide an overview of key immunopathogenetic processes underlying MG, and discuss on emerging biological drugs targeting them. We also discuss on future direction of research to address the need for patients\' stratification in endotypes according with genetic and molecular biomarkers for successful clinical decision making within precision medicine workflow.
摘要：
重症肌无力（MG）是一种由神经肌肉接头（NMJ）自身抗体引起的慢性致残性自身免疫性疾病，临床表现为眼部波动无力和早期疲劳，骨骼和延髓肌肉。尽管通常被认为是典型的自身免疫性疾病，MG是一个复杂且异质的条件，呈现可变的临床表型，可能是由于与不同免疫反应性相关的不同病理生理环境，症状分布，疾病严重程度,发病年龄,胸腺组织病理学和对治疗的反应。目前基于国际共识指南的MG治疗可以有效控制症状，但大多数患者无法达到完全缓解,需要终身免疫抑制(IS)治疗.此外，其中一部分对常规IS治疗是难治性的，强调需要更具体和量身定制的战略。精准医学是医学的新前沿，有望大大提高多种疾病的治疗成功率。包括自身免疫性疾病。在MG,B细胞激活,抗体再循环和补体系统对NMJ的损伤是至关重要的机制，创新生物药物的靶向作用已在临床试验中被证明是有效和安全的。从传统的IS到基于这些药物的新型精准医学方法的转变可以前瞻性地显着改善MG护理。在这次审查中,我们概述了MG背后的关键免疫病理学过程，并讨论针对它们的新兴生物药物。我们还讨论了未来的研究方向，以满足根据遗传和分子生物标志物对患者进行内生型分层的需求，以在精准医学工作流程中进行成功的临床决策。
