Changes in plasma itaconate elevation in early rheumatoid arthritis patients elucidates disease activity associated macrophage activation

Daly, R. et al. (2020) Changes in plasma itaconate elevation in early rheumatoid arthritis patients elucidates disease activity associated macrophage activation. Metabolites, 10(6), 241. (doi: 10.3390/metabo10060241) (PMID:32531990) (PMCID:PMC7344783)

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Abstract

Objective. To characterize changes in the plasma metabolic profile in newly diagnosed rheumatoid arthritis (RA) patients upon commencement of conventional disease modifying anti-rheumatic drug (cDMARD) therapy. Methods. Plasma samples collected in an early RA randomized 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 3 months post commencement of non-biologic cDMARD. Metabolites that changed in association with changes in the DAS44 score were identified at the 3 month timepoint. Results. A total of ten metabolites exhibited a clear correlation with 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 CRP. Conclusion. 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 an inflammatory disease in humans. Quantitative metabolic biomarker based tests of clinical change in state are feasible and should be developed around the itaconate pathway.

Item Type:Articles
Additional Information:Funding: The TaSER study was jointly funded by a Clinical Academic Fellowship from the Chief Scientist’s Office, Scottish Executive and an Investigator Initiated project grant from Pfizer UK. The metabolomics study was funded by an additional Investigator Initiated project grant from Pfizer UK. R.D. was funded by Wellcome (105614/Z/14/Z). M.P.B. is part of the Wellcome Centre for Molecular Parasitology funded by a core grant from Wellcome (104111/Z/14/Z).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McInnes, Professor Iain and Burgess, Dr Karl and Porter, Dr Duncan and Blackburn, Dr Gavin and Dale, Dr James and Mudaliar, Dr Manikhandan and Barrett, Professor Michael and Best, Cameron and Daly, Dr Ronan and Goodyear, Professor Carl
Authors: Daly, R., Blackburn, G., Best, C., Goodyear, C. S., Mudaliar, M., Burgess, K., Stirling, A., Porter, D., McInnes, I., Barrett, M. P., and Dale, J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Metabolites
Publisher:MDPI
ISSN:2218-1989
ISSN (Online):2218-1989
Copyright Holders:Copyright © 2020 The Authors
First Published:First published in Metabolites 10(6):241
Publisher Policy:Reproduced under a Creative Commons Licence
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
172121Funding SchemesAnna DominiczakWellcome Trust (WELLCOTR)105614/Z/14/ZInstitute of Cardiovascular & Medical Sciences
170547The Wellcome Centre for Molecular Parasitology ( Core Support )Andrew WatersWellcome Trust (WELLCOTR)104111/Z/14/ZRIII - Parasitology