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.

中文翻译：

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类风湿关节炎患者血浆衣康酸酯升高的变化阐明了与巨噬细胞活化有关的疾病活动。

在新诊断的类风湿关节炎（RA）患者中，开始常规的改变疾病的抗风湿药（cDMARD）治疗后，血浆代谢谱的变化得以表征。将早期RA随机策略研究（NCT00920478）中收集的血浆样品与临床（DAS）疾病活动性评估与肌肉骨骼超声评估（MSUS）进行比较，以决定治疗方案，然后进行非目标代谢组学分析。在非生物性cDMARD开始前和开始后三个月收集代谢谱。在三个月的时间点确定了与DAS44分数变化相关的代谢物。在cDMARD开始后，特别是衣康酸酯中，总共9种代谢物与DAS44得分的降低具有明显的相关性，其衍生的酸酐和衣康酸酯CoA的衍生物。衣康酸酯的增加与DAS44评分改善和C反应蛋白（CRP）降低有关。cDMARD的治疗作用引起血浆可检测代谢物的一致变化，进而使临床疾病活动与巨噬细胞有关。此类变化为RA发病机制提供了信息，并首次揭示了衣康酸酯生产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改变测试是可行的，应围绕衣康酸酯途径发展。进而将临床疾病活动与巨噬细胞联系起来。此类变化为RA发病机制提供了信息，并首次揭示了衣康酸酯生产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测试是可行的，应围绕衣康酸酯途径开展。进而将临床疾病活动与巨噬细胞联系起来。此类变化为RA发病机制提供了信息，并首次揭示了衣康酸酯的产生与人类炎症性疾病的消退之间的联系。基于定量代谢生物标志物的临床状态改变测试是可行的，应围绕衣康酸酯途径发展。