Pender Michael P
School of Medicine, The University of Queensland, Brisbane, Queensland, Australia.
Autoimmun Rev. 2009 Jun;8(7):563-8. doi: 10.1016/j.autrev.2009.01.017. Epub 2009 Jan 30.
It has been noted since 1981 that late primary infection with the Epstein-Barr virus (EBV) in adolescence or young adulthood can account for the epidemiology of multiple sclerosis (MS), including the association with higher socio-economic status, the latitudinal variation in prevalence, the effects of migration on the risk of acquiring MS, and the occurrence of clusters and epidemics. Virtually all (>99%) people with MS are EBV seropositive, suggesting that EBV infection is essential for the development of MS. The EBV-infected autoreactive B-cell hypothesis of autoimmunity published in 2003 proposes that, in genetically susceptible individuals, EBV-infected autoreactive B cells seed the target organ where they produce pathogenic autoantibodies and provide costimulatory survival signals to autoreactive T cells. This hypothesis makes several predictions, some of which have been verified in the case of MS, namely: the presence of EBV-infected B cells in the central nervous system; a beneficial response to B-cell depletion with rituximab; and decreased CD8(+) T-cell immunity to EBV-infected B cells. The hypothesis also predicts that chronic autoimmune diseases will respond to treatment which controls EBV infection. Thus it is proposed that vaccination against EBV will prevent MS, and that effective antiviral drugs will inhibit disease progression in people with MS and potentially be curative.
自1981年以来，人们已经注意到，在青少年期或青年期发生的爱泼斯坦-巴尔病毒（EBV）迟发性原发性感染可以解释多发性硬化症（MS）的流行病学特征，包括与较高社会经济地位的关联、患病率的纬度差异、移民对患MS风险的影响以及聚集性发病和流行的发生。几乎所有（>99%）的MS患者EBV血清学呈阳性，这表明EBV感染对于MS的发生至关重要。2003年发表的EBV感染引发自身免疫的自身反应性B细胞假说提出，在遗传易感个体中，EBV感染的自身反应性B细胞定植于靶器官，在那里它们产生致病性自身抗体，并为自身反应性T细胞提供共刺激存活信号。这一假说做出了几项预测，其中一些在MS病例中得到了验证，即：中枢神经系统中存在EBV感染的B细胞；对利妥昔单抗治疗B细胞减少有有益反应；以及针对EBV感染的B细胞的CD8(+) T细胞免疫降低。该假说还预测，慢性自身免疫性疾病将对控制EBV感染的治疗产生反应。因此，有人提出，接种EBV疫苗将预防MS，有效的抗病毒药物将抑制MS患者的疾病进展，并有可能治愈该病。
