Lower omega-3 fatty acids are associated with the presence of anti-cyclic citrullinated peptide autoantibodies in a population at risk for future rheumatoid arthritis: a nested case-control study

• Published in: Rheumatology (Oxford, England) Vol. 55; no. 2; pp. 367 - 376
• Main Authors: Gan, Ryan W, Young, Kendra A, Zerbe, Gary O, Demoruelle, M Kristen, Weisman, Michael H, Buckner, Jane H, Gregersen, Peter K, Mikuls, Ted R, O'Dell, James R, Keating, Richard M, Clare-Salzler, Michael J, Deane, Kevin D, Holers, V Michael, Norris, Jill M
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.02.2016
• Subjects: Arthritis, Rheumatoid - blood; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - epidemiology; Autoantibodies - blood; Autoantibodies - immunology; Basic and Translational Science; Enzyme-Linked Immunosorbent Assay; Fatty Acids, Omega-3 - administration & dosage; Fatty Acids, Omega-3 - pharmacokinetics; Female; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Peptides, Cyclic - blood; Peptides, Cyclic - immunology; Population Surveillance; Prospective Studies; Risk Factors; United States - epidemiology; United States; epidemiology; autoantibodies; rheumatoid arthritis
• ISSN: 1462-0324; 1462-0332
• DOI: 10.1093/rheumatology/kev266

The aim of this study was to investigate omega-3 fatty acid (FA) supplement use and omega-3 FAs in erythrocyte membranes [omega-3 FA % in erythrocyte membranes (RBC)] and their association with anti-CCP autoantibodies in a population without RA, but who are at genetic risk for RA. The multicentre Studies of the Etiology of RA (SERA) cohort includes RA-free subjects who are first-degree relatives of RA probands or are enriched with the HLA-DR4 allele. In a nested case-control study, 30 SERA cases were identified who were anti-CCP2 antibody positive. We further identified 47 autoantibody negative controls, frequency matched to cases on age at study visit, sex, race and study site. Anti-CCP2 status, self-reported omega-3 FA supplement use and omega-3 FA % in RBCs were obtained from a single visit. Anti-CCP2 positive cases were less likely than controls to report omega-3 FA supplement use (odds ratio: 0.14; 95% CI 0.03, 0.68). In addition, the likelihood of anti-CCP2 positivity was inversely associated with total omega-3 FA % in RBCs (odds ratio: 0.47; 95% CI 0.24, 0.92, for a s.d. increase). The inverse association between anti-CCP2 positivity and self-reported omega-3 FA supplement use and omega-3 FA % in RBCs suggests that omega-3 FAs may protect against the development of RA-related autoimmunity in pre-clinical RA.