Läderach Fabienne, Münz Christian
Viral Immunobiology, Institute of Experimental Immunology, University of Zurich, 8057 Zurich, Switzerland.
Microorganisms. 2021 Oct 21;9(11):2191. doi: 10.3390/microorganisms9112191.
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) for which both genetic and environmental risk factors have been identified. The strongest synergy among them exists between the MHC class II haplotype and infection with the Epstein Barr virus (EBV), especially symptomatic primary EBV infection (infectious mononucleosis) and elevated EBV-specific antibodies. In this review, we will summarize the epidemiological evidence that EBV infection is a prerequisite for MS development, describe altered EBV specific immune responses in MS patients, and speculate about possible pathogenic mechanisms for the synergy between EBV infection and the MS-associated MHC class II haplotype. We will also discuss how at least one of these mechanisms might explain the recent success of B cell-depleting therapies for MS. While a better mechanistic understanding of the role of EBV infection and its immune control during MS pathogenesis is required and calls for the development of innovative experimental systems to test the proposed mechanisms, therapies targeting EBV-infected B cells are already starting to be explored in MS patients.
多发性硬化症（MS）是一种中枢神经系统（CNS）的自身免疫性疾病，其遗传和环境风险因素均已明确。其中，MHC II类单倍型与爱泼斯坦-巴尔病毒（EBV）感染之间存在最强的协同作用，尤其是有症状的原发性EBV感染（传染性单核细胞增多症）以及EBV特异性抗体升高。在这篇综述中，我们将总结EBV感染是MS发病的先决条件这一流行病学证据，描述MS患者中EBV特异性免疫反应的改变，并推测EBV感染与MS相关MHC II类单倍型之间协同作用的可能致病机制。我们还将讨论这些机制中至少有一种如何解释近期MS B细胞耗竭疗法的成功。虽然需要对EBV感染及其在MS发病机制中的免疫控制作用有更深入的机制理解，并需要开发创新的实验系统来测试所提出的机制，但针对EBV感染B细胞的疗法已开始在MS患者中进行探索。
