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

Abstract

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.

Omega-3 fatty acids are associated with a lower prevalence of autoantibodies in shared epitope-positive subjects at risk for rheumatoid arthritis

“…In SE-positive participants, RF cases were more likely to have lower levels of total n-3 FA% in RBCs compared with controls (OR 0.26, 95% CI 0.09 to 0.77, p=0.02), while in SE-negative participants, no association was observed between total n-3 FA% in RBCs and RF (OR 0.92, 95% CI 0.48 to 1.77, p=0.81) (table 2). Similar to our previous report, 33 anti-CCP2 positivity was inversely associated with increasing total n-3 FA% in RBCs (OR 0.59, 95% CI 0.36 to 0.96) and EPA+DHA% in RBCs (OR 0.56, 95% CI 0.34 to 0.92) overall. However, when we examined effect modification by SE, we observed increasing total n-3 FA% in RBCs to be inversely associated with anti-CCP2 positivity in SE-positive participants (OR 0.44, 95% CI 0.21 to 0.93, p=0.03), but not in SE-negative participants (OR 0.77, 95% CI 0.41 to 1.45, p=0.42) (table 2).…”

“…Building upon our previous findings demonstrating an inverse association between n-3 FA and anti-CCP2 positivity in a population at risk for RA, 33 our current results show that n-3 FAs are also inversely associated with RF positivity, suggesting n-3 FAs may have a broader impact on RA-related autoimmunity in general. Furthermore, the association between n-3 FAs and RA-related autoimmunity was strongest in SE-positive participants.…”

“…As for n-3 FA% in RBCs and anti-CCP2, we observed an outright inverse association with anti-CCP2 positivity and n-3 FA, similar to our previous findings. 33 However, the observed interaction between n-3 FAs and SE on RF positivity prompted evaluation of a similar interaction with anti-CCP2. While the interaction term was not significant, we observed increasing n-3 FA% in RBCs were associated with a lower prevalence of anti-CCP2 positivity in SE-positive, but not SE-negative participants.…”

“…33 We selected an additional 27 SERA participants who were positive only for high titre RF by nephelometry (ie, a titre of >50 IU/mL), which was more than two times the standard SERA cut-off, and which has been shown to be a strong predictor for future RA. 36 We also selected an additional 10 anti-CCP2-positive cases for a total of 40 anti-CCP2-positive cases; cases could be positive for RF as well.…”

“…32 Furthermore, we found both n-3 FA supplement use and n-3 FA levels in RBC membranes were inversely associated with anti-CCP2 positivity in individuals without RA, but at risk for future RA. 33 However, it remains unclear whether n-3 FA exposure is associated with other RA-related autoantibodies, such as RF, and whether the association between n-3 FAs and RA-related autoantibodies is modified by SE, similar to the effect modification observed between SE and smoking on RA.…”