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ObjectivesLittle is known about the likelihood of developing inflammatory arthritis (IA) in individuals who screen autoantibody positive (aAb+) in a non-clinical research setting.MethodsWe screened for serum cyclic citrullinated peptide antibody (anti-CCP) and rheumatoid factor isotype aAbs in subjects who were at increased risk for rheumatoid arthritis (RA) because they are a first-degree relative of an individual with classified RA (n=1780). We evaluated combinations of aAbs and high titre aAbs, as defined by 2-times (2 x) the standard cut-off and an optimal cut-off, as predictors of our two outcomes, aAb+ persistence and incident IA.Results304 subjects (17.1%) tested aAb+; of those, 131 were IA-free and had at least one follow-up visit. Sixty-four per cent of these tested aAb+ again on their next visit. Anti-CCP+ at levels ≥2 x the standard cut-off was associated with 13-fold higher likelihood of aAb +persistence. During a median of 4.4 years (IQR: 2.2–7.2), 20 subjects (15.3%) developed IA. Among subjects that screened anti-CCP+ at ≥ 2 x or ≥an optimal cut-off, 32% and 26% had developed IA within 5 years, respectively. Both anti-CCP cut-offs conferred an approximate fourfold increased risk of future IA (HR 4.09 and HR 3.95, pConclusionsThese findings support that aAb screening in a non-clinical setting can identify RA-related aAb+ individuals, as well as levels and combinations of aAbs that are associated with higher risk for future IA. Monitoring for the development of IA in aAb+ individuals and similar aAb testing approaches in at-risk populations may identify candidates for prevention studies in RA.

ObjectivesPreviously, we found that omega-3 fatty acids (n-3 FAs) were inversely associated with anti-cyclic citrullinated peptide (anti-CCP) positivity in participants at risk for future rheumatoid arthritis (RA). We investigated whether n-3 FAs were also associated with rheumatoid factor (RF) positivity and whether these associations were modified by shared epitope (SE) positivity.MethodsThe Studies of the Etiology of RA (SERA) cohort includes RA-free participants who are at increased risk for RA. We conducted a nested case–control study (n=136) to determine the association between RF and anti-CCP2 positivity and n-3 FA percentage in erythrocyte membranes (n-3 FA% in red blood cells (RBCs)). Additionally, in the baseline visit of the SERA cohort (n=2166), we evaluated the association between reported n-3 FA supplement use and prevalence of RF and anti-CCP2. We assessed SE positivity as an effect modifier.ResultsIn the case–control study, increasing n-3 FA% in RBCs was inversely associated with RF positivity in SE-positive participants (OR 0.27, 95% CI 0.10 to 0.79), but not SE-negative participants. Similar associations were seen with anti-CCP positivity in SE-positive participants (OR 0.42, 95% CI 0.20 to 0.89), but not SE-negative participants. In the SERA cohort at baseline, n-3 FA supplement use was associated with a lower prevalence of RF positivity in SE-positive participants (OR 0.32, 95% CI 0.12 to 0.82), but not SE-negative participants; similar but non-significant trends were observed with anti-CCP2.ConclusionsThe potential protective effect of n-3 FAs on RA-related autoimmunity may be most pronounced in those who exhibit HLA class II genetic susceptibility to RA.

ObjectiveWe investigated whether rheumatoid arthritis (RA)-related autoantibodies were associated with systemic inflammation in a prospective cohort of first-degree relatives (FDRs) of RA probands, a population without RA but at increased risk for its future development.MethodsWe studied 44 autoantibody positive FDRs, of whom 29 were rheumatoid factor (RF) positive, 25 were positive for the high risk autoantibody profile (HRP), that is, positive for anti-cyclic citrullinated peptide and/or for at least two RF IgM, IgG or IgA isotypes, and nine FDRs who were positive for both; and 62 FDRs who were never autoantibody positive. Twenty-five cytokines/chemokines were measured using a bead-based assay in serum. As a comprehensive measure of inflammation, we calculated a Cytokine Score by summing all cytokine/chemokine levels, weighted by their regression coefficients for RA-autoantibody association. We compared C-reactive protein, individual cytokines/chemokines and Cytokine Score to the outcomes: positivity for RF and for the HRP using logistic regression.ResultsAdjusting for age, sex, ethnicity and ever smoking, the Cytokine Score and levels of IL-6 and IL-9 were associated with both RF and HRP. IL-2, granulocyte macrophage-colony stimulating factor (GM-CSF), and interferon (IFN)-γ were associated with HRP only. Associations between the Cytokine Score and RF and HRP positivity were replicated in an independent military personnel cohort.ConclusionsIn first-degree relatives of patients with RA, RA-related autoimmunity is associated with inflammation, as evidenced by associations with multiple cytokines and chemokines.

IntroductionStudies suggest that respiratory exposures including smoking, proximity to traffic and air pollution might be associated with development of rheumatoid arthritis (RA). RA-related autoantibodies are predictive of the development of RA.ObjectiveWe evaluated the relationship between RA-related autoantibodies and exposure to particulate matter (PM), a measure of air pollution of interest to health, in individuals without RA.MethodsThe Studies of the Etiology of Rheumatoid Arthritis (SERA) is a multicentre study following first-degree relatives (FDRs) of a proband with RA. FDRs are without the 1987 ACR (American College of Rheumatology) classifiable RA at enrolment and are followed for the development of RA-related autoimmunity. RA-related autoantibody outcomes as well as tender and swollen joint outcomes were assessed. Exposure to PM was assigned using ambient air pollution monitoring data and interpolated with inverse distance weighting spatial analyses using Geographic Information Systems. PM exposures were linked to FDR's residential zip codes.ResultsRA-related autoantibodies as well as tender or swollen joints are not associated with ambient PM concentrations.DiscussionWhile other respiratory exposures may be associated with increased risk of RA, our data suggest that ambient PM is not associated with autoantibodies and joint signs among individuals without RA, but at increased risk of developing RA.