Targeted metabolic profiling of the Tg197 mouse model reveals itaconic acid as a marker of Rheumatoid Arthritis.
File(s)Accepted Itaconic Acid Paper.docx (1.6 MB) Accepted itaconic acid supplementary data.docx (247.63 KB)
Accepted version
Accepted version
Author(s)
Type
Journal Article
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.
Date Issued
2016-10-05
Date Acceptance
2016-10-05
Citation
Journal of Proteome Research, 2016, 15 (12), pp.4579-4590
ISSN
1535-3907
Publisher
American Chemical Society
Start Page
4579
End Page
4590
Journal / Book Title
Journal of Proteome Research
Volume
15
Issue
12
Copyright Statement
© 2016 American Chemical Society. This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Proteome Research, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://dx.doi.org/10.1021/acs.jproteome.6b00654
Subjects
Biochemistry & Molecular Biology
06 Biological Sciences
03 Chemical Sciences
Publication Status
Published