Background/Purpose: Antibodies to citrullinated protein antigens (ACPA) can be elevated prior to onset of inflammatory arthritis (IA) and RA. However, understanding of factors related to development of ACPA, or transition from ACPA+ to clinically-apparent IA is limited. Omega-3 fatty acids (n-3 FA) have immunomodulating properties. In subjects at-risk for developing RA, we found higher levels of n-3 FA percentage in red blood cells (n-3 FA % in RBCs) were associated with a lower prevalence of positivity for ACPAs and rheumatoid factor (RF), suggesting n-3 FAs may be protective against development of autoantibodies. However, the relationship between n-3 FAs and IA in ACPA+ subjects remains unknown.  

Methods: At Colorado-based health fairs from 2008-2014, subjects without a previous diagnosis of RA were tested for serum ACPA using the commercial assay anti-cyclic citrullinated peptide 3 (Inova), and were recruited for follow-up research study visits. At their baseline study visit, they underwent symptom assessment and joint examination; the presence of IA and RA by 2010 criteria was established. Blood was also drawn to measure n-3 FA % in RBCs, a biomarker that reflects the average n-3 FA levels over the preceding ~2 months. The relationship between IA and RBC n-3 FA% was assessed using logistic regression.

Results: Fifty-two ACPA+ individuals without a prior diagnosis of RA were identified at health-fairs and agreed to participate in a follow-up baseline study visit; 41 were without IA, and 11 had IA that was previously undiagnosed (none were on disease modifying therapy). Subjects with IA at baseline were more likely to be smokers and report taking n-3 FA supplements, and test positive for RF and C-reactive protein (Table 1). Increasing total n-3 FA and DPA levels in RBCs (an n-3 FA generally synthesized through physiologic processes and not dietary) were associated with significantly lower odds of IA at baseline, adjusting for > 10 pack years and n-3 FA supplement use (both of which met confounding criteria)  (Table 2).

Conclusion:   We found that lower levels of n-3 FAs in individuals were associated with IA in this unique population of ACPA+ individuals. These extend our prior work by suggesting that in addition to having a potentially protective effect against autoimmunity, n-3 FAs may also be important in the transition to IA once an individual is ACPA+.  Our findings support the potential beneficial role of n-3 FAs in the preclinical state in RA, not only in decreasing the risk of developing ACPA and RF but also potentially decreasing the transition from an ACPA+ state to IA, findings which warrant further investigation.