Department of Neurology, Huashan Hospital, Fudan University, 200040, China.
Department of Neurology, Huashan Hospital, Fudan University, 200040, China.
Autoimmun Rev. 2019 Sep;18(9):102349. doi: 10.1016/j.autrev.2019.102349. Epub 2019 Jul 16.
Myasthenia gravis (MG) is a rare autoimmune disease characterized by muscle weakness and abnormal fatigability. Like many other autoimmune diseases, genetic contribution to MG has been studied where the HLA system appears to play the most vital role. Although many correlations have been revealed in these studies, the underlying mechanism for them is still in the veil. Based on current evidence, we propose two synergetic mechanisms underlying the MG predisposition via HLA. In brief, the first advocates specific MHC II-peptide patterns that influence the efficacy of antigen presentation, and the second emphasizes the role of classical MHC alleles in shaping the TCR repertoire for MG predisposition. Besides, possible explanations for unresolved or controversial MG-related epidemiological phenomenon or clinical problems are addressed as well. Then, we discuss three factors influencing the effect of HLA on MG: gender discrepancy, inflammatory microenvironment, and epigenetic regulation. Lastly, from a provisional angle, we introduce several precautious treatments for people highly predisposed to MG. Although this is a review focusing on MG, the underlying mechanisms might be applicable in other autoimmune diseases as well.
重症肌无力（MG）是一种罕见的自身免疫性疾病，其特征为肌肉无力和异常易疲劳。与许多其他自身免疫性疾病一样，MG 的遗传贡献已被研究，其中 HLA 系统似乎起着最重要的作用。尽管这些研究揭示了许多相关性，但它们的潜在机制仍不清楚。基于目前的证据，我们提出了两个通过 HLA 介导的 MG 易感性的协同机制。简而言之，第一个主张特定的 MHC II-肽模式，这些模式影响抗原呈递的效果，第二个强调经典 MHC 等位基因在塑造 MG 易感性的 TCR 库中的作用。此外，还针对未解决或有争议的 MG 相关流行病学现象或临床问题提出了可能的解释。然后，我们讨论了影响 HLA 对 MG 影响的三个因素：性别差异、炎症微环境和表观遗传调控。最后，从暂定的角度出发，我们介绍了几种针对 MG 高易感性人群的预防措施。虽然这是一篇聚焦 MG 的综述，但潜在机制也可能适用于其他自身免疫性疾病。
