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

Esteban A. Gomez, Romain A. Colas, Patricia R. Souza, Rebecca Hands, Myles J. Lewis, Conrad Bessant, Costantino Pitzalis and Jesmond Dalli ()
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Esteban A. Gomez: Queen Mary University of London
Romain A. Colas: Queen Mary University of London
Patricia R. Souza: Queen Mary University of London
Rebecca Hands: Queen Mary University of London
Myles J. Lewis: Queen Mary University of London
Conrad Bessant: Queen Mary University of London
Costantino Pitzalis: Queen Mary University of London
Jesmond Dalli: Queen Mary University of London

Nature Communications, 2020, vol. 11, issue 1, 1-13

Abstract: Abstract 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)A4 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.

Date: 2020
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DOI: 10.1038/s41467-020-19176-z

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