Targeted metabolic profiling of the Tg197 mouse model reveals itaconic acid as a marker of Rheumatoid Arthritis.

Michopoulos F, Karagianni N, Whalley NM, Firth MA, Nikolaou C, Wilson ID, Critchlow SE, Kollias G, Theodoridis GA. Targeted metabolic profiling of the Tg197 mouse model reveals itaconic acid as a marker of Rheumatoid Arthritis. J Proteome Res. 2016 Oct 5. PubMed PMID: 27704840.

Biomedcode coauthors a publication in the Journal of Proteome Research on the identification of a biomarker with translational value for the diagnosis and monitoring of rheumatoid arthritis disease and therapy.

Abstract: 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 non-invasive 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 (10mg/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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