Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
Multiple Sclerosis Research Centre, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.
J Neurovirol. 2021 Apr;27(2):260-271. doi: 10.1007/s13365-021-00951-7. Epub 2021 Mar 5.
Given the complexity of immune complex diseases including multiple sclerosis (MS) and the plausible interactions between different risk factors, delineating the interplay between them would be imperative. The current study aimed to evaluate the in vitro effects of Epstein-Barr virus (EBV) and vitamin D on immune response in MS patients and healthy controls. The status of vitamin D and EBV load was evaluated using multiple techniques. In vitro EBV-infected peripheral blood mononuclear cells (PBMCs), in the presence or absence of vitamin D, were checked for IL-10, IFN-γ, and vitamin D receptor. MS patients showed significantly higher plasma levels of 1,25-(OH)2D but not 25-OHD, increased EBV load, and lower levels of vitamin D receptor (VDR) expression compared with healthy controls. Interestingly, an inverse correlation was observed between VDR expression and EBV load in PBMCs. Indeed, the levels of IFN-γ and IL-10 production were significantly higher in supernatant collected from in vitro EBV-infected PBMCs in MS patients compared with controls. While all vitamin D-treated PBMCs showed reduced levels of IFN-γ production, in vitro treatment of vitamin D showed no influence in IL-10 production. EBV and vitamin D were found to exert opposite in vitro effects on immune dysregulation in these patients. Our results highlight the complex interactions of different risk factors with immune system.
鉴于包括多发性硬化症 (MS) 在内的免疫复合物疾病的复杂性,以及不同风险因素之间可能存在的相互作用,阐明它们之间的相互作用至关重要。本研究旨在评估 EB 病毒 (EBV) 和维生素 D 对 MS 患者和健康对照者免疫反应的体外影响。采用多种技术评估维生素 D 和 EBV 载量的状态。在存在或不存在维生素 D 的情况下,检查 EBV 感染的外周血单核细胞 (PBMC) 中的 IL-10、IFN-γ 和维生素 D 受体。与健康对照组相比,MS 患者的血浆 1,25-(OH)2D 水平明显升高,但 25-OHD 水平没有升高,EBV 载量升高,维生素 D 受体 (VDR) 表达水平降低。有趣的是,PBMC 中 VDR 表达与 EBV 载量呈负相关。事实上,与对照组相比,从 MS 患者体外 EBV 感染的 PBMC 中收集的上清液中 IFN-γ 和 IL-10 的产生水平显着升高。虽然所有用维生素 D 处理的 PBMC 均显示 IFN-γ 产生水平降低,但维生素 D 的体外治疗对 IL-10 的产生没有影响。在这些患者中,EBV 和维生素 D 被发现对免疫失调具有相反的体外作用。我们的研究结果强调了不同风险因素与免疫系统之间的复杂相互作用。