Blood pro-resolving mediators are linked with synovial pathology and are predictive of DMARD responsiveness in rheumatoid arthritis

Biomarkers are needed for predicting the effectiveness of disease modifying antirheumatic drugs (DMARDs). Here, using functional lipid mediator profiling and deeply phenotyped patients with early rheumatoid arthritis (RA), we observe that peripheral blood  specialized pro-resolving mediator (SPM) co...

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Autores principales: Gomez, Esteban A., Colas, Romain A., Souza, Patricia R., Hands, Rebecca, Lewis, Myles J., Bessant, Conrad, Pitzalis, Costantino, Dalli, Jesmond
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
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Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591509/
https://www.ncbi.nlm.nih.gov/pubmed/33110080
http://dx.doi.org/10.1038/s41467-020-19176-z
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author Gomez, Esteban A.
Colas, Romain A.
Souza, Patricia R.
Hands, Rebecca
Lewis, Myles J.
Bessant, Conrad
Pitzalis, Costantino
Dalli, Jesmond
author_facet Gomez, Esteban A.
Colas, Romain A.
Souza, Patricia R.
Hands, Rebecca
Lewis, Myles J.
Bessant, Conrad
Pitzalis, Costantino
Dalli, Jesmond
author_sort Gomez, Esteban A.
collection PubMed
description Biomarkers are needed for predicting the effectiveness of disease modifying antirheumatic drugs (DMARDs). Here, using functional lipid mediator profiling and deeply phenotyped patients with early rheumatoid arthritis (RA), we observe that peripheral blood  specialized pro-resolving mediator (SPM) concentrations are linked with both DMARD responsiveness and disease pathotype. Machine learning analysis demonstrates that baseline plasma concentrations of resolvin D4, 10S, 17S-dihydroxy-docosapentaenoic acid, 15R-Lipoxin (LX)A(4) and n-3 docosapentaenoic-derived Maresin 1 are predictive of DMARD responsiveness at 6 months. Assessment of circulating SPM concentrations 6-months after treatment initiation establishes that differences between responders and non-responders are maintained, with a decrease in SPM concentrations in patients resistant to DMARD therapy. These findings elucidate the potential utility of  plasma SPM concentrations as biomarkers of DMARD responsiveness in RA.
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spelling pubmed-75915092020-11-10 Blood pro-resolving mediators are linked with synovial pathology and are predictive of DMARD responsiveness in rheumatoid arthritis Gomez, Esteban A. Colas, Romain A. Souza, Patricia R. Hands, Rebecca Lewis, Myles J. Bessant, Conrad Pitzalis, Costantino Dalli, Jesmond Nat Commun Article Biomarkers are needed for predicting the effectiveness of disease modifying antirheumatic drugs (DMARDs). Here, using functional lipid mediator profiling and deeply phenotyped patients with early rheumatoid arthritis (RA), we observe that peripheral blood  specialized pro-resolving mediator (SPM) concentrations are linked with both DMARD responsiveness and disease pathotype. Machine learning analysis demonstrates that baseline plasma concentrations of resolvin D4, 10S, 17S-dihydroxy-docosapentaenoic acid, 15R-Lipoxin (LX)A(4) and n-3 docosapentaenoic-derived Maresin 1 are predictive of DMARD responsiveness at 6 months. Assessment of circulating SPM concentrations 6-months after treatment initiation establishes that differences between responders and non-responders are maintained, with a decrease in SPM concentrations in patients resistant to DMARD therapy. These findings elucidate the potential utility of  plasma SPM concentrations as biomarkers of DMARD responsiveness in RA. Nature Publishing Group UK 2020-10-27 /pmc/articles/PMC7591509/ /pubmed/33110080 http://dx.doi.org/10.1038/s41467-020-19176-z Text en © The Author(s) 2020 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Gomez, Esteban A.
Colas, Romain A.
Souza, Patricia R.
Hands, Rebecca
Lewis, Myles J.
Bessant, Conrad
Pitzalis, Costantino
Dalli, Jesmond
Blood pro-resolving mediators are linked with synovial pathology and are predictive of DMARD responsiveness in rheumatoid arthritis
title Blood pro-resolving mediators are linked with synovial pathology and are predictive of DMARD responsiveness in rheumatoid arthritis
title_full Blood pro-resolving mediators are linked with synovial pathology and are predictive of DMARD responsiveness in rheumatoid arthritis
title_fullStr Blood pro-resolving mediators are linked with synovial pathology and are predictive of DMARD responsiveness in rheumatoid arthritis
title_full_unstemmed Blood pro-resolving mediators are linked with synovial pathology and are predictive of DMARD responsiveness in rheumatoid arthritis
title_short Blood pro-resolving mediators are linked with synovial pathology and are predictive of DMARD responsiveness in rheumatoid arthritis
title_sort blood pro-resolving mediators are linked with synovial pathology and are predictive of dmard responsiveness in rheumatoid arthritis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591509/
https://www.ncbi.nlm.nih.gov/pubmed/33110080
http://dx.doi.org/10.1038/s41467-020-19176-z
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