Dyer Zoe, Tscharke David, Sutton Ian, Massey Jennifer
Blood Stem Cell and Cancer Research Group, St Vincent's Centre for Applied Medical Research Darlinghurst NSW Australia.
St. Vincent's Clinical School, Faculty of Medicine University of New South Wales (UNSW) Darlinghurst NSW Australia.
Clin Transl Immunology. 2023 Feb 23;12(2):e1437. doi: 10.1002/cti2.1437. eCollection 2023.
Therapy for relapsing-remitting multiple sclerosis (MS) has advanced dramatically despite incomplete understanding of the cause of the condition. Current treatment involves inducing broad effects on immune cell populations with consequent off-target side effects, and no treatment can completely prevent disability progression. Further therapeutic advancement will require a better understanding of the pathobiology of MS. Interest in the role of Epstein-Barr virus (EBV) in multiple sclerosis has intensified based on strong epidemiological evidence of an association between EBV seroprevalence and MS. Hypotheses proposed to explain the biological relationship between EBV and MS include molecular mimicry, EBV immortalised autoreactive B cells and infection of glial cells by EBV. Examining the interaction between EBV and immunotherapies that have demonstrated efficacy in MS offers clues to the validity of these hypotheses. The efficacy of B cell depleting therapies could be consistent with a hypothesis that EBV-infected B cells drive MS; however, loss of T cell control of B cells does not exacerbate MS. A number of MS therapies invoke change in EBV-specific T cell populations, but pathogenic EBV-specific T cells with cross-reactivity to CNS antigen have not been identified. Immune reconstitution therapies induce EBV viraemia and expansion of EBV-specific T cell clones, but this does not correlate with relapse. Much remains unknown regarding the role of EBV in MS pathogenesis. We discuss future translational research that could fill important knowledge gaps.
尽管对复发缓解型多发性硬化症（MS）的病因了解尚不完整，但针对该疾病的治疗已取得了显著进展。目前的治疗方法是对免疫细胞群体产生广泛影响，从而导致非靶向副作用，而且没有任何治疗方法能够完全阻止残疾进展。进一步的治疗进展需要更好地理解MS的病理生物学。基于EB病毒（EBV）血清阳性率与MS之间存在关联的强有力流行病学证据，人们对EBV在多发性硬化症中的作用的兴趣日益浓厚。为解释EBV与MS之间的生物学关系而提出的假说包括分子模拟、EBV永生化自身反应性B细胞以及EBV感染神经胶质细胞。研究EBV与已在MS中证明有效的免疫疗法之间的相互作用，为这些假说的有效性提供了线索。B细胞清除疗法的疗效可能与EBV感染的B细胞驱动MS这一假说一致；然而，T细胞对B细胞控制的丧失并不会加重MS。许多MS疗法会引起EBV特异性T细胞群体的变化，但尚未鉴定出与中枢神经系统抗原有交叉反应的致病性EBV特异性T细胞。免疫重建疗法会诱导EBV病毒血症和EBV特异性T细胞克隆的扩增，但这与复发并无关联。关于EBV在MS发病机制中的作用，仍有许多未知之处。我们讨论了未来可能填补重要知识空白的转化研究。
