类风湿性关节炎
医学
关节炎
衣康酸
疾病
英夫利昔单抗
转基因小鼠
药理学
免疫学
转基因
内科学
生物
化学
生物化学
聚合物
有机化学
基因
共聚物
作者
Filippos Michopoulos,Niki Karagianni,Nichola Whalley,Mike Firth,Christoforos Nikolaou,Ian D. Wilson,Susan E. Critchlow,George Kollias,Georgios Theodoridis
标识
DOI:10.1021/acs.jproteome.6b00654
摘要
Rheumatoid arthritis is a progressive, highly debilitating disease where early diagnosis, enabling rapid clinical intervention, would provide obvious benefits to patients, healthcare systems, and society. Novel biomarkers that enable noninvasive early diagnosis of the onset and progression of the disease provide one route to achieving this goal. Here a metabolic profiling method has been applied to investigate disease development in the Tg197 arthritis mouse model. Hind limb extract profiling demonstrated clear differences in metabolic phenotypes between control (wild type) and Tg197 transgenic mice and highlighted raised concentrations of itaconic acid as a potential marker of the disease. These changes in itaconic acid concentrations were moderated or indeed reversed when the Tg197 mice were treated with the anti-hTNF biologic infliximab (10 mg/kg twice weekly for 6 weeks). Further in vitro studies on synovial fibroblasts obtained from healthy wild-type, arthritic Tg197, and infliximab-treated Tg197 transgenic mice confirmed the association of itaconic acid with rheumatoid arthritis and disease-moderating drug effects. Preliminary indications of the potential value of itaconic acid as a translational biomarker were obtained when studies on K4IM human fibroblasts treated with hTNF showed an increase in the concentrations of this metabolite.
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