Although genetic and epidemiological evidence indicates vitamin D insufficiency contributes to multiple sclerosis (MS), and serum levels of vitamin D increase on treatment with cholecalciferol, recent metanalyses indicate that this vitamin D form does not ameliorate disease. Genetic variation in genes regulating vitamin D, and regulated by vitamin D, affect MS risk. We evaluated if the expression of vitamin D responsive MS risk genes could be used to assess vitamin D response in immune cells. Peripheral blood mononuclear cells (PBMCs) were isolated from healthy controls and people with MS treated with dimethyl fumarate. We assayed changes in expression of vitamin D responsive MS risk (VDRMS) genes in response to treatment with 25 hydroxy vitamin D in the presence or absence of inflammatory stimuli. Expression of CYP24A1 and other VDRMS genes was significantly altered in PBMCs treated with vitamin D in the homeostatic and inflammatory models. Gene expression in MS samples had similar responses to controls, but lower initial expression of the risk genes. Vitamin D treatment abrogated these differences. Expression of CYP24A1 and other MS risk genes in blood immune cells indicate vitamin D response and could enable assessment of immunological response to vitamin D in clinical trials and on therapy.

尽管遗传学和流行病学证据表明维生素 D 不足会导致多发性硬化症 (MS)，并且胆钙化醇治疗后血清维生素 D 水平会升高，但最近的荟萃分析表明这种维生素 D 形式不会改善疾病。调节维生素 D 和受维生素 D 调节的基因的遗传变异会影响 MS 风险。我们评估了维生素 D 反应性 MS 风险基因的表达是否可用于评估免疫细胞中的维生素 D 反应。外周血单核细胞 (PBMC) 分离自健康对照和接受富马酸二甲酯治疗的 MS 患者。我们检测了在存在或不存在炎症刺激的情况下，维生素 D 反应性 MS 风险 (VDRMS) 基因表达对 25 羟基维生素 D 治疗的反应变化。在体内平衡和炎症模型中，用维生素 D 处理的 PBMC 中 CYP24A1 和其他 VDRMS 基因的表达发生显着改变。MS 样本中的基因表达与对照有相似的反应，但风险基因的初始表达较低。维生素 D 治疗消除了这些差异。CYP24A1 和其他 MS 风险基因在血液免疫细胞中的表达表明维生素 D 反应，并且可以在临床试验和治疗中评估对维生素 D 的免疫反应。