BACKGROUND Despite compelling evidence that cigarette smoking impacts the risk of developing multiple sclerosis (MS), little is known about smoking-associated changes in the primary exposed lung cells of patients. OBJECTIVES We aimed to examine molecular changes occurring in bronchoalveolar lavage (BAL) cells from MS patients in relation to smoking and in comparison to healthy controls (HCs). METHODS We profiled DNA methylation in BAL cells from female MS (n = 17) and HC (n = 22) individuals, using Illumina Infinium EPIC and performed RNA-sequencing in non-smokers. RESULTS The most prominent changes were found in relation to smoking, with 1376 CpG sites (adjusted P < 0.05) differing between MS smokers and non-smokers. Approximately 30% of the affected genes overlapped with smoking-associated changes in HC, leading to a strong common smoking signature in both MS and HC after gene ontology analysis. Smoking in MS patients resulted in additional discrete changes related to neuronal processes. Methylome and transcriptome analyses in non-smokers suggest that BAL cells from MS patients display very subtle (not reaching adjusted P < 0.05) but concordant changes in genes connected to reduced transcriptional/translational processes and enhanced cellular motility. CONCLUSIONS Our study provides insights into the impact of smoking on lung inflammation and immunopathogenesis of MS.

中文翻译：

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与吸烟有关的多发性硬化患者支气管肺泡细胞的甲基化组和转录组特征

背景尽管有令人信服的证据表明吸烟会影响患多发性硬化症 (MS) 的风险，但人们对与吸烟相关的患者主要暴露肺细胞的变化知之甚少。目的 我们旨在检查 MS 患者的支气管肺泡灌洗 (BAL) 细胞中发生的与吸烟相关的分子变化，并与健康对照 (HC) 进行比较。方法 我们使用 Illumina Infinium EPIC 分析了来自女性 MS（n = 17）和 HC（n = 22）个体的 BAL 细胞中的 DNA 甲基化，并在非吸烟者中进行了 RNA 测序。结果 最显着的变化与吸烟有关，MS 吸烟者和非吸烟者之间有 1376 个 CpG 位点（调整后的 P < 0.05）不同。大约 30% 的受影响基因与吸烟相关的 HC 变化重叠，在基因本体分析后导致 MS 和 HC 中强烈的共同吸烟特征。MS 患者的吸烟导致与神经元过程相关的额外离散变化。非吸烟者的甲基化组和转录组分析表明，来自 MS 患者的 BAL 细胞表现出非常微妙（未达到调整后的 P < 0.05），但与转录/翻译过程减少和细胞运动性增强相关的基因发生一致变化。结论 我们的研究为吸烟对 MS 肺部炎症和免疫发病机制的影响提供了见解。非吸烟者的甲基化组和转录组分析表明，来自 MS 患者的 BAL 细胞表现出非常微妙（未达到调整后的 P < 0.05），但与转录/翻译过程减少和细胞运动性增强相关的基因发生一致变化。结论 我们的研究为吸烟对 MS 肺部炎症和免疫发病机制的影响提供了见解。非吸烟者的甲基化组和转录组分析表明，来自 MS 患者的 BAL 细胞表现出非常微妙（未达到调整后的 P < 0.05），但与转录/翻译过程减少和细胞运动性增强相关的基因发生一致变化。结论 我们的研究为吸烟对 MS 肺部炎症和免疫发病机制的影响提供了见解。