It is unclear whether smoking interacts with different aspects of Epstein–Barr virus (EBV) infection with regard to multiple sclerosis (MS) risk. We aimed to investigate whether smoking acts synergistically with elevated EBNA-1 antibody levels or infectious mononucleosis (IM) history regarding MS risk. Two Swedish population-based case–control studies were used (6,340 cases and 6,219 matched controls). Subjects with different smoking, EBNA-1 and IM status were compared regarding MS risk, by calculating odds ratios (OR) with 95% confidence intervals (CI) employing logistic regression. Potential interaction on the additive scale was evaluated by calculating the attributable proportion due to interaction (AP). Current and past smokers had higher EBNA-1 antibody levels than never smokers (p < 0.0001). There was an additive interaction between current smoking and high EBNA-1 antibody levels (AP 0.3, 95% CI 0.2–0.4), but not between past smoking and high EBNA-1 antibody levels (AP 0.01, 95% CI − 0.1 to 0.1), with regard to MS risk. An interaction also occurred between current smoking and IM history (AP 0.2, 95% CI 0.004–0.4), but not between past smoking and IM history (AP − 0.06, 95% CI − 0.4 to 0.3). Current smoking increases EBNA-1 antibody levels and acts synergistically with both aspects of EBV infection to increase MS risk, indicating that there is at least one pathway to disease in which both risk factors are involved.

目前尚不清楚吸烟是否与多发性硬化症（MS）风险与爱泼斯坦-巴尔病毒（EBV）感染的不同方面相互作用。我们的目的是调查吸烟与EBNA-1抗体水平升高或与MS风险有关的感染性单核细胞增多症（IM）历史是否具有协同作用。进行了两项瑞典基于人群的病例对照研究（6,340例病例和6,219例匹配对照）。通过使用逻辑回归计算具有95％置信区间（CI）的优势比（OR），比较了吸烟，EBNA-1和IM状态不同的受试者的MS风险。通过计算归因于相互作用的比例（AP）来评估添加剂规模上的潜在相互作用。当前和过去的吸烟者比从未吸烟者具有更高的EBNA-1抗体水平（p <0.0001）。当前吸烟与高EBNA-1抗体水平（AP 0.3，95％CI 0.2-0.4）之间存在加性相互作用，但过去吸烟与高EBNA-1抗体水平之间（AP 0.01，95％CI-0.1至0.1之间没有累加相互作用） ），关于MS风险。当前吸烟与IM历史之间也发生了相互作用（AP 0.2，95％CI 0.004–0.4），但过去吸烟与IM历史之间没有相互作用（AP-0.06，95％CI-0.4至0.3）。当前吸烟会增加EBNA-1抗体水平，并与EBV感染的两个方面协同作用，从而增加MS风险，这表明至少存在一条涉及这两种风险因素的疾病途径。当前吸烟与IM历史之间也发生了相互作用（AP 0.2，95％CI 0.004–0.4），但过去吸烟与IM历史之间没有相互作用（AP-0.06，95％CI-0.4至0.3）。当前吸烟会增加EBNA-1抗体水平，并与EBV感染的两个方面协同作用，从而增加MS风险，这表明至少存在一条涉及这两种风险因素的疾病途径。当前吸烟与IM历史之间也发生了相互作用（AP 0.2，95％CI 0.004–0.4），但过去吸烟与IM历史之间没有相互作用（AP-0.06，95％CI-0.4至0.3）。当前吸烟会增加EBNA-1抗体水平，并与EBV感染的两个方面协同作用，从而增加MS风险，这表明至少存在一条涉及这两种风险因素的疾病途径。