Neuroimmunology Group, Nuffield Department of Clinical Neurosciences, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
Ann N Y Acad Sci. 2018 Feb;1413(1):143-153. doi: 10.1111/nyas.13592. Epub 2018 Jan 29.
Antibodies to the acetylcholine receptor (AChR) have been recognized for over 40 years and have been important in the diagnosis of myasthenia gravis (MG), and its recognition in patients of different ages and thymic pathologies. The 10-20% of patients who do not have AChR antibodies are now known to comprise different subgroups, the most commonly reported of which is patients with antibodies to muscle-specific kinase (MuSK). The use of cell-based assays has extended the repertoire of antibody tests to clustered AChRs, low-density lipoprotein receptor-related protein 4, and agrin. Autoantibodies against intracellular targets, namely cortactin, titin, and ryanodine receptor (the latter two being associated with the presence of thymoma), may also be helpful as biomarkers in some patients. IgG4 MuSK antibodies are clearly pathogenic, but the coexisting IgG1, IgG2, and IgG3 antibodies, collectively, have effects that question the dominance of IgG4 as the sole pathologic factor in MuSK MG. After a brief historical review, we define the different subgroups and summarize the antibody characteristics. Experiments to demonstrate the in vitro and in vivo pathogenic roles of MuSK antibodies are discussed.
乙酰胆碱受体 (AChR) 抗体已被认识超过 40 年，在重症肌无力 (MG) 的诊断中具有重要意义，并且在不同年龄和胸腺病理的患者中也有识别。现在已知，10-20% 没有 AChR 抗体的患者包含不同的亚组，其中最常见的是肌肉特异性激酶 (MuSK) 抗体患者。基于细胞的检测方法将抗体检测的范围扩展到聚集的 AChR、低密度脂蛋白受体相关蛋白 4 和聚集素。针对细胞内靶标的自身抗体，即肌动蛋白结合蛋白 cortactin、titin 和肌浆网钙释放通道蛋白受体 (后两者与胸腺瘤的存在有关)，在某些患者中也可能作为生物标志物有用。IgG4 MuSK 抗体显然具有致病性，但共存的 IgG1、IgG2 和 IgG3 抗体具有质疑 IgG4 作为 MuSK MG 唯一病理因素的主导地位的作用。在简要回顾历史之后，我们定义了不同的亚组并总结了抗体特征。讨论了证明 MuSK 抗体在体外和体内的致病作用的实验。
