Background: Epstein–Barr virus (EBV) infection is thought to play a central role in the development of multiple sclerosis (MS). If causal, it represents a target for interventions to reduce MS risk. Objective: To examine the evidence for interaction between EBV and other risk factors, and explore mechanisms via which EBV infection may influence MS risk. Methods: Pubmed was searched using the terms ‘multiple sclerosis’ AND ‘Epstein Barr virus’, ‘multiple sclerosis’ AND EBV, ‘clinically isolated syndrome’ AND ‘Epstein Barr virus’ and ‘clinically isolated syndrome’ AND EBV. All abstracts were reviewed for possible inclusion. Results: A total of 262 full-text papers were reviewed. There was evidence of interaction on the additive scale between anti-EBV antibody titre and HLA genotype (attributable proportion due to interaction (AP) = 0.48, p < 1 × 10−4). Previous infectious mononucleosis (IM) was associated with increased odds ratio (OR) of MS in HLA-DRB1*1501 positive but not HLA-DRB1*1501 negative persons. Smoking was associated with a greater risk of MS in those with high anti-EBV antibodies (OR = 2.76) but not low anti-EBV antibodies (OR = 1.16). No interaction between EBV and risk factors was found on a multiplicative scale. Conclusion: EBV appears to interact with at least some established MS risk factors. The mechanism via which EBV influences MS risk remains unknown.

中文翻译：

---

爱泼斯坦-巴尔病毒、多发性硬化症和其他危险因素之间关联的系统评价和荟萃分析

背景：爱泼斯坦-巴尔病毒 (EBV) 感染被认为在多发性硬化症 (MS) 的发展中起核心作用。如果是因果关系，它代表干预措施以降低 MS 风险的目标。目的：检查 EBV 与其他危险因素相互作用的证据，并探讨 EBV 感染可能影响 MS 风险的机制。方法：使用术语“多发性硬化症”和“爱泼斯坦巴尔病毒”、“多发性硬化症”和 EBV、“临床分离综合征”和“爱泼斯坦巴尔病毒”和“临床分离综合征”以及 EBV 搜索 Pubmed。所有摘要都经过审查，以确保可能包含在内。结果：共审阅全文262篇。有证据表明抗 EBV 抗体滴度和 HLA 基因型之间的累加量表存在相互作用（相互作用的归因比例 (AP) = 0.48，p < 1 × 10−4)。先前的传染性单核细胞增多症 (IM) 与 HLA-DRB1*1501 阳性而不是 HLA-DRB1*1501 阴性人群中 MS 的比值比 (OR) 增加有关。在抗 EBV 抗体高 (OR = 2.76) 但抗 EBV 抗体低 (OR = 1.16) 的患者中，吸烟与 MS 风险增加相关。在乘法尺度上未发现 EBV 与风险因素之间的相互作用。结论：EBV 似乎与至少一些已确定的 MS 风险因素相互作用。EBV 影响 MS 风险的机制仍然未知。在乘法尺度上未发现 EBV 与风险因素之间的相互作用。结论：EBV 似乎与至少一些已确定的 MS 风险因素相互作用。EBV 影响 MS 风险的机制仍然未知。在乘法尺度上未发现 EBV 与风险因素之间的相互作用。结论：EBV 似乎与至少一些已确定的 MS 风险因素相互作用。EBV 影响 MS 风险的机制仍然未知。