Center for Brain Research, Medical University of Vienna, Vienna, Austria.
Curr Opin Neurol. 2019 Jun;32(3):313-319. doi: 10.1097/WCO.0000000000000685.
Research on multiple sclerosis (MS) pathogenesis and therapy is to a large extent driven by results obtained in experimental autoimmune encephalomyelitis (EAE). This approach provided deep insights into the mechanism of brain inflammation and immune mediated tissue injury and, thus, most of our currently established therapies for MS patients have been developed with profound contributions of experimental autoimmune research. Recent data, which are summarized in this review article, however, show important differences between EAE and MS.
EAE models perfectly reproduce a disease, now called myelin oligodendrocyte glycoprotein (MOG) antibody-associated inflammatory demyelinating disease, which, however, is different from classical MS. In MS, the inflammatory reaction in the brain is dominated by CD8 T-lymphocyte and CD20 B cells. Demyelination in MS appears to be triggered by soluble factors, produced by T cells and/or B cells, which are different from anti-MOG antibodies seen in EAE, and induce widespread MS like primary demyelination and tissue damage associated with oxidative injury, mitochondrial damage and subsequent 'virtual' hypoxia.
To define the antigenic target of the inflammatory reaction, the nature of the inflammatory response and the mechanisms of tissue injury are key topics of ongoing MS research.
多发性硬化症（MS）发病机制和治疗的研究在很大程度上是基于实验性自身免疫性脑脊髓炎（EAE）的研究结果。这一方法深入了解了脑炎症和免疫介导的组织损伤的机制，因此，我们目前为 MS 患者开发的大多数治疗方法都得益于实验性自身免疫研究的深远贡献。然而，最近总结在这篇综述文章中的数据表明，EAE 和 MS 之间存在重要差异。
EAE 模型完美地再现了一种现在被称为髓鞘少突胶质细胞糖蛋白（MOG）抗体相关的炎症性脱髓鞘疾病，但与经典的 MS 不同。在 MS 中，大脑中的炎症反应主要由 CD8 T 淋巴细胞和 CD20 B 细胞引起。MS 中的脱髓鞘似乎是由 T 细胞和/或 B 细胞产生的可溶性因子触发的，这些因子与 EAE 中所见的抗 MOG 抗体不同，并诱导广泛的 MS 样原发性脱髓鞘和与氧化损伤、线粒体损伤和随后的“虚拟”缺氧相关的组织损伤。
为了确定炎症反应的抗原靶点、炎症反应的性质和组织损伤的机制，是正在进行的 MS 研究的关键主题。
