Serum test for secretory component-containing anti-citrullinated protein antibodies as a novel prognostic tool in rheumatoid arthritis at-risk subjects.

Individuals with autoantibodies against citrullinated proteins (ACPA) and musculoskeletal symptoms face increased risk of developing rheumatoid arthritis (RA). There are knowledge gaps concerning who will develop disease, and predictors of RA onset are highly warranted. A mucosal origin hypothesis in RA is gaining increasing support, for instance by a previous study showing that secretory component-containing ACPA (SC ACPA) in the circulation are prognostic for RA onset. This study aimed to confirm the prognostic value of serum SC ACPA in a large cohort of symptomatic at-risk subjects and to establish a cutoff level for the prognostic use of SC ACPA testing. Baseline sera from an observational prospective cohort of IgG ACPA positive individuals with musculoskeletal complaints (Karolinska cohort, n = 266) were tested for SC ACPA by ELISA. SC ACPA levels were increased among subjects subsequently developing arthritis (n = 100, median 62 arbitrary units (AU)/mL) compared to those who did not (n = 166, median 40 AU/mL; p < 0.001). A cutoff level for the optimal discrimination concerning future arthritis onset was established by Youden's index, resulting in 81 subjects (30 %) testing positive for SC ACPA, whereof 45 (56 %) progressed to arthritis. Among those testing negative (n = 185), significantly fewer progressed (n = 55, 30 %; p < 0.001). This cutoff was then tested in the previously studied at-risk cohort (n = 82), revealing similar prognostic performance in both cohorts (sensitivity 45 % and 41 %; specificity 78 % and 81 %). We conclude that serum SC ACPA testing is of potential clinical value in symptomatic at-risk subjects and strengthens the mucosal association in RA development.