当前位置: X-MOL 学术Front. Mol. Neurosci. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Myasthenia Gravis With Antibodies Against Muscle Specific Kinase: An Update on Clinical Features, Pathophysiology and Treatment
Frontiers in Molecular Neuroscience ( IF 4.8 ) Pub Date : 2020-08-03 , DOI: 10.3389/fnmol.2020.00159
Michelangelo Cao 1 , Inga Koneczny 2 , Angela Vincent 1
Affiliation  

Muscle Specific Kinase myasthenia gravis (MuSK-MG) is an autoimmune disease that impairs neuromuscular transmission leading to generalized muscle weakness. Compared to the more common myasthenia gravis with antibodies against the acetylcholine receptor (AChR), MuSK-MG affects mainly the bulbar and respiratory muscles, with more frequent and severe myasthenic crises. Treatments are usually less effective with the need for prolonged, high doses of steroids and other immunosuppressants to control symptoms. Under physiological condition, MuSK regulates a phosphorylation cascade which is fundamental for the development and maintenance of postsynaptic AChR clusters at the neuromuscular junction (NMJ). Agrin, secreted by the motor nerve terminal into the synaptic cleft, binds to low density lipoprotein receptor-related protein 4 (LRP4) which activates MuSK. In MuSK-MG, monovalent MuSK-IgG4 autoantibodies block MuSK-LRP4 interaction preventing MuSK activation and leading to the dispersal of AChR clusters. Lower levels of divalent MuSK IgG1, 2, and 3 antibody subclasses are also present but their contribution to the pathogenesis of the disease remains controversial. This review aims to provide a detailed update on the epidemiological and clinical features of MuSK-MG, focusing on the pathophysiological mechanisms and the latest indications regarding the efficacy and safety of different treatment options.



中文翻译:

具有针对肌肉特异性激酶的抗体的重症肌无力:临床特征、病理生理学和治疗的最新进展

肌肉特异性激酶重症肌无力 (MuSK-MG) 是一种自身免疫性疾病,可损害神经肌肉传递,导致全身肌肉无力。与更常见的带有乙酰胆碱受体 (AChR) 抗体的重症肌无力相比,MuSK-MG 主要影响延髓和呼吸肌,具有更频繁和更严重的肌无力危象。由于需要长时间、高剂量的类固醇和其他免疫抑制剂来控制症状,治疗通常效果较差。在生理条件下,MuSK 调节磷酸化级联反应,这是神经肌肉接头 (NMJ) 突触后 AChR 簇的发育和维持的基础。集聚蛋白,由运动神经末梢分泌到突触间隙,与激活 MuSK 的低密度脂蛋白受体相关蛋白 4 (LRP4) 结合。在 MuSK-MG 中,单价 MuSK-IgG4 自身抗体阻断 MuSK-LRP4 相互作用,阻止 MuSK 激活并导致 AChR 簇的分散。也存在较低水平的二价 MuSK IgG1、2 和 3 抗体亚类,但它们对疾病发病机制的贡献仍存在争议。本综述旨在提供有关 MuSK-MG 流行病学和临床特征的详细更新,重点关注病理生理机制和不同治疗方案有效性和安全性的最新适应症。和 3 个抗体亚类也存在,但它们对疾病发病机制的贡献仍有争议。本综述旨在提供有关 MuSK-MG 流行病学和临床特征的详细更新,重点关注病理生理机制和不同治疗方案有效性和安全性的最新适应症。和 3 个抗体亚类也存在,但它们对疾病发病机制的贡献仍有争议。本综述旨在提供有关 MuSK-MG 流行病学和临床特征的详细更新,重点关注病理生理机制和不同治疗方案有效性和安全性的最新适应症。

更新日期:2020-09-02
down
wechat
bug