Pender Michael P
Faculty of Medicine The University of Queensland Brisbane QLD Australia.
Department of Neurology Royal Brisbane and Women's Hospital Brisbane QLD Australia.
Clin Transl Immunology. 2020 Apr 6;9(4):e1116. doi: 10.1002/cti2.1116. eCollection 2020 Apr.
Bipolar disorder (BD) is a chronic disease characterised by episodes of major depression and episodes of mania or hypomania, with a worldwide prevalence of 2.4%. The cause of BD is unknown. Here, I propose the hypothesis that BD is a chronic autoimmune disease caused by Epstein-Barr virus (EBV) infection of autoreactive B cells. It is postulated that EBV-infected autoreactive B cells accumulate in the brain where they provide costimulatory survival signals to autoreactive T cells and differentiate into plasma cells producing pathogenic autoantibodies targeting brain components such as the N-methyl-D-aspartate receptor. It is also proposed that the accumulation of EBV-infected autoreactive B cells in the brain is a consequence of a genetically determined defect in the ability of CD8 T cells to control EBV infection. The theory is supported by studies indicating that autoimmunity, EBV infection and CD8 T-cell deficiency all have roles in the pathogenesis of BD. According to the hypothesis, BD should be able to be treated by EBV-specific T-cell therapy and to be prevented by vaccination against EBV in early childhood. Exposure to sunlight or appropriate artificial light should also be beneficial in BD by augmenting CD8 T-cell control of EBV infection.
双相情感障碍（BD）是一种慢性疾病，其特征为重度抑郁发作以及躁狂或轻躁狂发作，全球患病率为2.4%。BD的病因尚不清楚。在此，我提出一个假说，即BD是一种由自身反应性B细胞感染爱泼斯坦-巴尔病毒（EBV）引起的慢性自身免疫性疾病。据推测，被EBV感染的自身反应性B细胞在大脑中积聚，在那里它们为自身反应性T细胞提供共刺激存活信号，并分化为浆细胞，产生针对大脑成分（如N-甲基-D-天冬氨酸受体）的致病性自身抗体。还提出，大脑中被EBV感染的自身反应性B细胞的积聚是CD8 T细胞控制EBV感染能力的基因决定缺陷的结果。该理论得到了多项研究的支持，这些研究表明自身免疫、EBV感染和CD8 T细胞缺陷在BD的发病机制中均起作用。根据这一假说，BD应该能够通过EBV特异性T细胞疗法进行治疗，并能够通过在幼儿期接种EBV疫苗来预防。暴露于阳光或适当的人造光下，通过增强CD8 T细胞对EBV感染的控制，对BD也应该是有益的。
