Department of Neurology Johns Hopkins University School of Medicine Baltimore Maryland.
Ann Clin Transl Neurol. 2018 Oct 30;6(1):33-45. doi: 10.1002/acn3.676. eCollection 2019 Jan.
Identify metabolic changes produced by dimethyl fumarate (DMF) treatment and link them to immunological effects.
We enrolled 18 MS patients and obtained blood prior to DMF and 6 months postinitiation. We also enrolled 18 healthy controls for comparison. We performed global metabolomics on plasma and used weighted correlation network analysis (WGCNA) to identify modules of correlated metabolites. We identified modules that changed with treatment, followed by targeted metabolomics to corroborate changes identified in global analyses. We correlated changes in metabolite modules and individual metabolites with changes in immunological parameters.
We identified alterations in lipid metabolism after DMF treatment - increases in two modules (phospholipids, lysophospholipids and plasmalogens) and reduction in one module (saturated and poly-unsaturated fatty acids) eigen-metabolite values (all < 0.05). Change in the fatty acid module was greater in participants who developed lymphopenia and was strongly associated with both reduction in absolute lymphocyte counts (=0.65; = 0.005) and change in CD8+ T cell subsets. We also noted significant correlation of change in lymphocyte counts with multiple fatty acid levels (measured by targeted or untargeted methods).
This study demonstrates that DMF treatment alters lipid metabolism and that changes in fatty acid levels are related to DMF-induced immunological changes.
鉴定富马酸二甲酯（DMF）治疗引起的代谢变化，并将其与免疫作用联系起来。
我们纳入了 18 名 MS 患者，并在 DMF 治疗前和治疗后 6 个月采集了血液样本。我们还纳入了 18 名健康对照者进行比较。我们对血浆进行了全局代谢组学分析，并使用加权相关网络分析（WGCNA）来鉴定相关代谢物模块。我们鉴定了与治疗相关的变化模块，然后进行靶向代谢组学分析以证实全局分析中鉴定的变化。我们将代谢物模块和个体代谢物的变化与免疫参数的变化相关联。
我们发现 DMF 治疗后脂质代谢发生了改变——两个模块（磷脂、溶血磷脂和血浆类脂）的含量增加，一个模块（饱和脂肪酸和多不饱和脂肪酸）的特征代谢物值降低（均 <0.05）。在发生淋巴细胞减少的参与者中，脂肪酸模块的变化更大，并且与绝对淋巴细胞计数的减少（=0.65；=0.005）和 CD8+T 细胞亚群的变化密切相关。我们还注意到，淋巴细胞计数的变化与多种脂肪酸水平（通过靶向或非靶向方法测量）显著相关。
这项研究表明，DMF 治疗会改变脂质代谢，脂肪酸水平的变化与 DMF 诱导的免疫变化有关。
