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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| Format: | Article |
| Language: | English |
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MDPI AG
2020-06-01
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| Series: | Metabolites |
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| Online Access: | https://www.mdpi.com/2218-1989/10/6/241 |
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| author | Rónán Daly Gavin Blackburn Cameron Best Carl S. Goodyear Manikhandan Mudaliar Karl Burgess Anne Stirling Duncan Porter Iain B. McInnes Michael P. Barrett James Dale |
| author_facet | Rónán Daly Gavin Blackburn Cameron Best Carl S. Goodyear Manikhandan Mudaliar Karl Burgess Anne Stirling Duncan Porter Iain B. McInnes Michael P. Barrett James Dale |
| author_sort | Rónán Daly |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T19:15:59Z |
| format | Article |
| id | doaj.art-5e35c46d3e0b43d5828fdb46fd292b77 |
| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-03-10T19:15:59Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-5e35c46d3e0b43d5828fdb46fd292b772023-11-20T03:25:26ZengMDPI AGMetabolites2218-19892020-06-0110624110.3390/metabo10060241Changes in Plasma Itaconate Elevation in Early Rheumatoid Arthritis Patients Elucidates Disease Activity Associated Macrophage ActivationRónán Daly0Gavin Blackburn1Cameron Best2Carl S. Goodyear3Manikhandan Mudaliar4Karl Burgess5Anne Stirling6Duncan Porter7Iain B. McInnes8Michael P. Barrett9James Dale10Glasgow Polyomics, University of Glasgow, Glasgow G61 1BD, UKGlasgow Polyomics, University of Glasgow, Glasgow G61 1BD, UKInstitute of Infection, Immunity and Inflammation, University of Glasgow, 120 University Place, Glasgow G12 8TA, UKInstitute of Infection, Immunity and Inflammation, University of Glasgow, 120 University Place, Glasgow G12 8TA, UKGlasgow Polyomics, University of Glasgow, Glasgow G61 1BD, UKGlasgow Polyomics, University of Glasgow, Glasgow G61 1BD, UKDepartment of Rheumatology, Gartnavel General Hospital, Glasgow G12 0YN, UKInstitute of Infection, Immunity and Inflammation, University of Glasgow, 120 University Place, Glasgow G12 8TA, UKInstitute of Infection, Immunity and Inflammation, University of Glasgow, 120 University Place, Glasgow G12 8TA, UKGlasgow Polyomics, University of Glasgow, Glasgow G61 1BD, UKInstitute of Infection, Immunity and Inflammation, University of Glasgow, 120 University Place, Glasgow G12 8TA, UKChanges 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.https://www.mdpi.com/2218-1989/10/6/241rheumatoid arthritisDMARDmacrophageitaconateinflammationliquid chromatography–mass spectrometry (LC-MS) |
| spellingShingle | Rónán Daly Gavin Blackburn Cameron Best Carl S. Goodyear Manikhandan Mudaliar Karl Burgess Anne Stirling Duncan Porter Iain B. McInnes Michael P. Barrett James Dale Changes in Plasma Itaconate Elevation in Early Rheumatoid Arthritis Patients Elucidates Disease Activity Associated Macrophage Activation Metabolites rheumatoid arthritis DMARD macrophage itaconate inflammation liquid chromatography–mass spectrometry (LC-MS) |
| 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 | rheumatoid arthritis DMARD macrophage itaconate inflammation liquid chromatography–mass spectrometry (LC-MS) |
| url | https://www.mdpi.com/2218-1989/10/6/241 |
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