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Objectives: To investigate the occurrence and dynamics of secretory component-containing antibodies towards citrullinated proteins (SC ACPA) in plasma from pre-symptomatic individuals subsequently developing rheumatoid arthritis (RA).

Methods: We studied 319 individuals who had donated plasma prior to RA onset (median predating time 4.7 years), whereof 181 also donated samples after diagnosis. One hundred individuals were randomly selected from the same biobank cohorts to serve as controls. SC ACPA, total secretory IgA (TSIgA) and IgG ACPA were analysed in plasma by enzyme-linked immunoassays.

Results: Circulating SC ACPA levels in pre-symptomatic individuals and RA patients were significantly increased compared with controls [median (interquartile range) 108 (108), 179 (248) and 12.5 (537) AU/ml, respectively; P < 0.001], and SC ACPA levels in RA patients were significantly increased compared with pre-symptomatic individuals (P < 0.001). SC ACPA increased, in terms of both levels and proportion of positive samples, closer to symptom onset and diagnosis. TSIgA was not elevated compared with controls either during the pre-dating time or after diagnosis. The earliest detected SC ACPA positive sample was 9 years before symptom onset, as compared with 11 years for IgG ACPA. Only two pre-dating samples were positive for SC ACPA and negative for IgG ACPA.

Conclusions: Circulating SC ACPA responses arise and magnify during the asymptomatic phase of disease development in a subgroup of RA patients. This suggests mucosal involvement prior to both symptom onset and subsequent arthritis. As mirrored in the circulation, however, SC ACPA does not seem to precede the IgG ACPA response.