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Association of Lipid Mediators With Development of Future Incident Inflammatory Arthritis in an Anti–Citrullinated Protein Antibody–Positive Population
Author(s) -
Polinski Kristen J.,
Bemis Elizabeth A.,
Yang Fan,
Crume Tessa,
Demoruelle M. Kristen,
Feser Marie,
Seifert Jennifer,
O’Dell James R.,
Mikuls Ted R.,
Weisman Michael H.,
Gregersen Peter K.,
Keating Richard M.,
Buckner Jane,
Reisdorph Nichole,
Deane Kevin D.,
ClareSalzler Michael,
Holers V. Michael,
Norris Jill M.
Publication year - 2021
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.41631
Subject(s) - medicine , rheumatoid arthritis , hazard ratio , proinflammatory cytokine , autoantibody , prospective cohort study , immunology , cohort , proportional hazards model , arthritis , population , rheumatoid factor , cohort study , confidence interval , antibody , inflammation , environmental health
Objective To determine the association of polyunsaturated fatty acid (PUFA)–derived lipid mediators with progression from rheumatoid arthritis (RA)–related autoimmunity to inflammatory arthritis (IA). Methods We conducted a prospective cohort study using data from the Studies of the Etiology of Rheumatoid Arthritis (SERA). SERA enrolled first‐degree relatives (FDRs) of individuals with RA (FDR cohort) and individuals who screened positive for RA‐related autoantibodies at health fairs (screened cohort). We followed up 133 anti–cyclic citrullinated peptide 3.1 (anti‐CCP3.1)–positive participants, 29 of whom developed IA. Lipid mediators selected a priori were quantified from stored plasma samples using liquid chromatography tandem mass spectrometry. We fit multivariable Cox proportional hazards models for each lipid mediator as a time‐varying variable. For lipid mediators found to be significantly associated with IA, we then examined interleukin‐1β (IL‐1β), IL‐6, IL‐8, and tumor necrosis factor (TNF) as potential statistical mediators. Results For every 1 natural log pg/ml increase in the circulating plasma levels of proinflammatory 5‐HETE, the risk of developing IA increased by 241% (hazard ratio 2.41 [95% confidence interval 1.43–4.07]) after adjusting for age at baseline, cohort (FDR or screened), and shared epitope status. The models examining 15‐HETE and 17‐HDHA had the same trend but did not reach significance. We did not find evidence that the association between 5‐HETE and IA risk was influenced by the proinflammatory cytokines tested. Conclusion In a prospective cohort of anti‐CCP–positive individuals, higher levels of 5‐HETE, an important precursor to proinflammatory leukotrienes, is associated with subsequent IA. Our findings highlight the potential significance of these PUFA metabolites in pre‐RA populations.