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Changes in Plasma Itaconate Elevation in Early Rheumatoid Arthritis Patients Elucidates Disease Activity Associated Macrophage Activation

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 cli...

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Autores principales: Daly, Rónán, Blackburn, Gavin, Best, Cameron, Goodyear, Carl S., Mudaliar, Manikhandan, Burgess, Karl, Stirling, Anne, Porter, Duncan, McInnes, Iain B., Barrett, Michael P., Dale, James
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7344783/
https://www.ncbi.nlm.nih.gov/pubmed/32531990
http://dx.doi.org/10.3390/metabo10060241
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author Daly, Rónán
Blackburn, Gavin
Best, Cameron
Goodyear, Carl S.
Mudaliar, Manikhandan
Burgess, Karl
Stirling, Anne
Porter, Duncan
McInnes, Iain B.
Barrett, Michael P.
Dale, James
author_facet Daly, Rónán
Blackburn, Gavin
Best, Cameron
Goodyear, Carl S.
Mudaliar, Manikhandan
Burgess, Karl
Stirling, Anne
Porter, Duncan
McInnes, Iain B.
Barrett, Michael P.
Dale, James
author_sort Daly, Rónán
collection PubMed
description 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.
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spelling pubmed-73447832020-07-09 Changes in Plasma Itaconate Elevation in Early Rheumatoid Arthritis Patients Elucidates Disease Activity Associated Macrophage Activation Daly, Rónán Blackburn, Gavin Best, Cameron Goodyear, Carl S. Mudaliar, Manikhandan Burgess, Karl Stirling, Anne Porter, Duncan McInnes, Iain B. Barrett, Michael P. Dale, James Metabolites Article 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. MDPI 2020-06-10 /pmc/articles/PMC7344783/ /pubmed/32531990 http://dx.doi.org/10.3390/metabo10060241 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Daly, Rónán
Blackburn, Gavin
Best, Cameron
Goodyear, Carl S.
Mudaliar, Manikhandan
Burgess, Karl
Stirling, Anne
Porter, Duncan
McInnes, Iain B.
Barrett, Michael P.
Dale, James
Changes in Plasma Itaconate Elevation in Early Rheumatoid Arthritis Patients Elucidates Disease Activity Associated Macrophage Activation
title Changes in Plasma Itaconate Elevation in Early Rheumatoid Arthritis Patients Elucidates Disease Activity Associated Macrophage Activation
title_full Changes in Plasma Itaconate Elevation in Early Rheumatoid Arthritis Patients Elucidates Disease Activity Associated Macrophage Activation
title_fullStr Changes in Plasma Itaconate Elevation in Early Rheumatoid Arthritis Patients Elucidates Disease Activity Associated Macrophage Activation
title_full_unstemmed Changes in Plasma Itaconate Elevation in Early Rheumatoid Arthritis Patients Elucidates Disease Activity Associated Macrophage Activation
title_short Changes in Plasma Itaconate Elevation in Early Rheumatoid Arthritis Patients Elucidates Disease Activity Associated Macrophage Activation
title_sort changes in plasma itaconate elevation in early rheumatoid arthritis patients elucidates disease activity associated macrophage activation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7344783/
https://www.ncbi.nlm.nih.gov/pubmed/32531990
http://dx.doi.org/10.3390/metabo10060241
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