The Stanley Research Program at Sheppard Pratt, Baltimore, MD.
The Stanley Neurovirology Laboratory, Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, MD.
Schizophr Bull. 2019 Sep 11;45(5):1112-1119. doi: 10.1093/schbul/sby164.
Epstein-Barr virus (EBV) is a highly prevalent human herpesvirus capable of infecting the central nervous system and establishing persistent infection.
We employed solid phase immunoassay techniques to measure immunoglobulin G (IgG) class antibodies to EBV virions and defined proteins in 432 individuals with schizophrenia and 311 individuals without a history of a psychiatric disorder. Western blot testing was performed to document reactivity to specific EBV proteins. Polygenic risk for schizophrenia was calculated from genome sequencing arrays. Levels of antibodies between the groups were compared by multivariate analyses incorporating clinical, genetic, and demographic measures.
Individuals with schizophrenia had marked elevations in the levels of antibodies to EBV virions as compared to the control population. Further analyses indicated increased levels of reactivity to EBV-viral capsid antibody (VCA) but not to EBV nuclear antigen-1 (EBNA-1) or to other human herpesviruses. Western blot analysis confirmed increased reactivity to VCA proteins in the group of individuals with schizophrenia and documented a lack of increased levels of antibodies to EBNA-1. Genetic analyses indicated an additive effect of increased levels of antibodies to EBV virions and genetic susceptibility to schizophrenia, with individuals with elevated levels of both type of markers having a greater than 8.5-fold odds of a schizophrenia diagnosis.
Individuals with schizophrenia have increased levels of antibodies to some but not all EBV proteins indicating an aberrant response to EBV infection. This aberrant response may contribute to the immunopathology of schizophrenia and related disorders.
爱泼斯坦-巴尔病毒（EBV）是一种高度流行的人类疱疹病毒，能够感染中枢神经系统并建立持续性感染。
我们采用固相免疫测定技术，测量了 432 名精神分裂症患者和 311 名无精神病史个体的针对 EBV 病毒粒子和特定蛋白的 IgG 类抗体。通过 Western blot 检测来记录针对特定 EBV 蛋白的反应性。通过基因组测序阵列计算精神分裂症的多基因风险。通过多元分析比较了两组之间的抗体水平，该分析纳入了临床、遗传和人口统计学措施。
与对照组相比，精神分裂症患者针对 EBV 病毒粒子的抗体水平明显升高。进一步的分析表明，针对 EBV 衣壳抗原（VCA）的反应性增加，但针对 EBV 核抗原-1（EBNA-1）或其他人类疱疹病毒的反应性没有增加。Western blot 分析证实了精神分裂症组中 VCA 蛋白的反应性增加，并记录到缺乏针对 EBNA-1 的抗体水平增加。遗传分析表明，针对 EBV 病毒粒子的抗体水平升高和精神分裂症遗传易感性存在累加效应，具有这两种标志物升高的个体患精神分裂症的几率大于 8.5 倍。
精神分裂症患者针对某些而非所有 EBV 蛋白的抗体水平升高，表明对 EBV 感染存在异常反应。这种异常反应可能导致精神分裂症和相关疾病的免疫病理学。
