Expansion of alternative autoantibodies does not follow the evolution of anti-citrullinated protein antibodies in preclinical rheumatoid arthritis - An analysis in at-risk first-degree relatives.

BACKGROUND Co-occurrence of autoantibodies specific for more than one autoimmune disease is widely prevalent in rheumatoid arthritis (RA) patients. To understand the prevalence of polyautoimmunity in preclinical RA, we performed a comprehensive autoantibody assessment in a First Nations (FN) cohort of at-risk first-degree relatives (FDR) of RA patients, a subset of whom subsequently developed RA (Progressors). METHODS Venous blood was collected at scheduled visits from all study participants and serum was stored at -20°C. Hs-CRP, anti-citrullinated protein antibodies (ACPA), and autoantibodies were determined using commercially available ELISA kits. Rheumatoid factor (RF) was detected by nephelometry. Anti-nuclear autoantibodies (ANA) were identified using HEp2 indirect immunofluorescence assay (IFA) and classified according to international consensus nomenclature as various anti-cell (AC) patterns. RESULTS We observed positive ANA reactivity (≥1:80) in 78.9% of our study cohort, which was either a homogenous, fine-speckled (AC-1 and AC-4) or mixed IFA pattern. Importantly, the AC-4 and mixed ANA pattern was also observed in Progressors at the time of disease onset. While all the RA patients showed a high prevalence of arthritis-associated autoantibodies, they also had a high prevalence of ENA-positive autoantibodies to other autoantigens. In FDR, we did not observe any increase in serum autoreactivity to non-arthritis autoantigens, either cross-sectionally or in longitudinally collected Progressor samples prior to RA onset. CONCLUSION While alternative autoimmunity and ANA positivity is widely prevalent in FN population, including asymptomatic, seronegative FDR, expansion of alternative autoimmunity in FDR does not occur in parallel to ACPA expansion and is restricted to established RA patients.