Myasthenia Gravis: Autoantibody Specificities and Their Role in MG Management.
Myasthenia Gravis: Autoantibody Specificities and Their Role in MG Management.
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DOI：
10.3389/fneur.2020.596981
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发表时间：
2020
影响因子：
3.4
通讯作者：
Tzartos SJ
中科院分区：
文献类型：
--
作者：
Lazaridis K;Tzartos SJ
重症肌无力(MG)是最常见的影响神经肌肉接头的自身免疫性疾病，以骨骼肌无力和疲劳性为特征。它是由针对神经肌肉接头蛋白的自身抗体引起的；大约85%的MG患者有抗肌乙酰胆碱受体(AChR-MG)的自身抗体，而大约5%的MG患者有抗肌肉特异性激酶(Musk-MG)的自身抗体。在其余约10%的患者中，AChR和Musk抗体(血清阴性MG，SN-MG)的经典诊断方法均未发现自身抗体。由于血清学检测对于疾病诊断是相对容易和非侵入性的，因此改进检测已知自身抗体的方法或发现新的自身抗体特异性以减少SN-MG并促进类似疾病的鉴别诊断是至关重要的。放射免疫沉淀分析(RIPA)是检测MG抗体的主要方法，但在过去的几年里，使用基于细胞的分析(CBAS)或改进的高灵敏度RIPAS，已经能够检测出既往SN-MG患者的自身抗体。这导致更多的患者被鉴定出对经典抗原AChR和Musk以及第三种MG自身抗原低密度脂蛋白受体相关蛋白4(LRP4)的抗体，同时在一些MG患者中发现了针对其他细胞外或细胞内靶点的抗体，如集聚蛋白、Kv1.4钾通道、Q胶原蛋白、肌动蛋白、兰尼定受体和皮质素。由于靶向自身抗原在一定程度上决定了临床表现、预后和治疗反应，因此血清学检测不仅对初始诊断是必不可少的，而且对监测治疗效果也是必不可少的。重要的是，了解MG患者的自身抗体谱可以允许更有效的个性化治疗方法。在过去的几年里，在开发抗原特异性治疗方面取得了重大进展，仅针对参与自身免疫反应的特定免疫细胞或自身抗体。在这篇综述中，我们将介绍新的敏感的自身抗体检测方法的发展，新的MG自身抗原的鉴定，以及改进抗原特异性治疗的意义。这些进展增加了我们对MG病理的了解，通过提供更快、更准确的诊断和更好的疾病管理，提高了患者的生活质量。
Myasthenia gravis (MG) is the most common autoimmune disorder affecting the neuromuscular junction, characterized by skeletal muscle weakness and fatigability. It is caused by autoantibodies targeting proteins of the neuromuscular junction; ~85% of MG patients have autoantibodies against the muscle acetylcholine receptor (AChR-MG), whereas about 5% of MG patients have autoantibodies against the muscle specific kinase (MuSK-MG). In the remaining about 10% of patients no autoantibodies can be found with the classical diagnostics for AChR and MuSK antibodies (seronegative MG, SN-MG). Since serological tests are relatively easy and non-invasive for disease diagnosis, the improvement of methods for the detection of known autoantibodies or the discovery of novel autoantibody specificities to diminish SN-MG and to facilitate differential diagnosis of similar diseases, is crucial. Radioimmunoprecipitation assays (RIPA) are the staple for MG antibody detection, but over the past years, using cell-based assays (CBAs) or improved highly sensitive RIPAs, it has been possible to detect autoantibodies in previously SN-MG patients. This led to the identification of more patients with antibodies to the classical antigens AChR and MuSK and to the third MG autoantigen, the low-density lipoprotein receptor-related protein 4 (LRP4), while antibodies against other extracellular or intracellular targets, such as agrin, Kv1.4 potassium channels, collagen Q, titin, the ryanodine receptor and cortactin have been found in some MG patients. Since the autoantigen targeted determines in part the clinical manifestations, prognosis and response to treatment, serological tests are not only indispensable for initial diagnosis, but also for monitoring treatment efficacy. Importantly, knowing the autoantibody profile of MG patients could allow for more efficient personalized therapeutic approaches. Significant progress has been made over the past years toward the development of antigen-specific therapies, targeting only the specific immune cells or autoantibodies involved in the autoimmune response. In this review, we will present the progress made toward the development of novel sensitive autoantibody detection assays, the identification of new MG autoantigens, and the implications for improved antigen-specific therapeutics. These advancements increase our understanding of MG pathology and improve patient quality of life by providing faster, more accurate diagnosis and better disease management.
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