Lipidome profile predictive of disease evolution and activity in rheumatoid arthritis

초록

Rheumatoid arthritis: Changes in lipid profile mark disease activity The profile of lipid metabolites changes according to the different phases of rheumatoid arthritis (RA) activity, providing potential biomarkers for tracking and treating the disease. Lipid metabolites play diverse roles in the body, including acting as signaling molecules for inflammation. Wan-Uk Kim (Catholic University of Korea, Seoul), Sung Won Kwon (Seoul National University), and co-workers across South Korea analyzed the lipid profiles (or 'lipidomes') of joint fluid and serum samples were taken from 79 patients (42 from active RA, 19 from sustained remission, 18 from preclinical RA) at the preclinical, active, and remission phases of RA. The lipidome of joint fluid was significantly disrupted both in preclinical and active RA, and the extent of disruption matched the severity of disease. There were marked differences in the serum lipidome between active and remission phases. Monitoring lipidome profiles could prove invaluable for early diagnosis, and may inform future precision therapeutics. 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.

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