Daly Rónán, Blackburn Gavin, Best Cameron, Goodyear Carl S, Mudaliar Manikhandan, Burgess Karl, Stirling Anne, Porter Duncan, McInnes Iain B, Barrett Michael P, Dale James
Glasgow Polyomics, University of Glasgow, Glasgow G61 1BD, UK.
Institute of Infection, Immunity and Inflammation, University of Glasgow, 120 University Place, Glasgow G12 8TA, UK.
Metabolites. 2020 Jun 10;10(6):241. doi: 10.3390/metabo10060241.
Changes in the plasma metabolic profile were characterised in newly diagnosed rheumatoid arthritis (RA) patients upon commencement of conventional disease-modifying anti-rheumatic drug (cDMARD) therapy. Plasma samples collected in an early RA randomised strategy study (NCT00920478) that compared clinical (DAS) disease activity assessment with musculoskeletal ultrasound assessment (MSUS) to drive treatment decisions were subjected to untargeted metabolomic analysis. Metabolic profiles were collected at pre- and three months post-commencement of nonbiologic cDMARD. Metabolites that changed in association with changes in the DAS44 score were identified at the three-month timepoint. A total of nine metabolites exhibited a clear correlation with a reduction in DAS44 score following cDMARD commencement, particularly itaconate, its derived anhydride and a derivative of itaconate CoA. Increasing itaconate correlated with improved DAS44 score and decreasing levels of C-reactive protein (CRP). cDMARD treatment effects invoke consistent changes in plasma detectable metabolites, that in turn implicate clinical disease activity with macrophages. Such changes inform RA pathogenesis and reveal for the first time a link between itaconate production and resolution of inflammatory disease in humans. Quantitative metabolic biomarker-based tests of clinical change in state are feasible and should be developed around the itaconate pathway.
在新诊断的类风湿关节炎（RA）患者开始使用传统改善病情抗风湿药物（cDMARD）治疗时，对其血浆代谢谱变化进行了表征。在一项早期类风湿关节炎随机策略研究（NCT00920478）中收集的血浆样本，该研究比较了临床（DAS）疾病活动评估与肌肉骨骼超声评估（MSUS）以指导治疗决策，并对样本进行了非靶向代谢组学分析。在开始使用非生物cDMARD治疗前及治疗后三个月收集代谢谱。在三个月时间点识别出与DAS44评分变化相关的代谢物。共有9种代谢物在开始使用cDMARD后与DAS44评分降低呈现明显相关性，特别是衣康酸、其衍生酸酐和衣康酸辅酶A的衍生物。衣康酸增加与DAS44评分改善及C反应蛋白（CRP）水平降低相关。cDMARD治疗效果引起血浆中可检测代谢物的一致变化，这反过来暗示了巨噬细胞与临床疾病活动的关系。这些变化为类风湿关节炎的发病机制提供了信息，并首次揭示了衣康酸产生与人类炎症性疾病消退之间的联系。基于定量代谢生物标志物的临床状态变化检测是可行的，应围绕衣康酸途径开展相关研究。
