Abstract
Lipid mediators are crucial for the pathogenesis of rheumatoid arthritis (RA); however, global analyses have not been undertaken to systematically define the lipidome underlying the dynamics of disease evolution, activation, and resolution. Here, we performed untargeted lipidomics analysis of synovial fluid and serum from RA patients at different disease activities and clinical phases (preclinical phase to active phase to sustained remission). We found that the lipidome profile in RA joint fluid was severely perturbed and that this correlated with the extent of inflammation and severity of synovitis on ultrasonography. The serum lipidome profile of active RA, albeit less prominent than the synovial lipidome, was also distinguishable from that of RA in the sustained remission phase and from that of noninflammatory osteoarthritis. Of note, the serum lipidome profile at the preclinical phase of RA closely mimicked that of active RA. Specifically, alterations in a set of lysophosphatidylcholine, phosphatidylcholine, ether-linked phosphatidylethanolamine, and sphingomyelin subclasses correlated with RA activity, reflecting treatment responses to anti-rheumatic drugs when monitored serially. Collectively, these results suggest that analysis of lipidome profiles is useful for identifying biomarker candidates that predict the evolution of preclinical to definitive RA and could facilitate the assessment of disease activity and treatment outcomes.
Original language | English |
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Pages (from-to) | 143-155 |
Number of pages | 13 |
Journal | Experimental and Molecular Medicine |
Volume | 54 |
Issue number | 2 |
DOIs | |
State | Published - Feb 2022 |
Bibliographical note
Funding Information:This work was supported by grants from the National Research Foundation of Korea (NRF), funded by the Ministry of Education, Science and Technology (NRF-2015R1A3A2032927, and NRF-2018R1D1A1B07045491) and the Ministry of Science and ICT (NRF-2018R1A5A2024425).
Funding Information:
We thank Eun Goo Lee and Ji Won Lee for excellent technical support. We also thank the members of the Center for Integrative Rheumatoid Transcriptomics and Dynamics (CIRAD) at the Catholic University of Korea for their assistance.
Publisher Copyright:
© 2022, The Author(s).