Anti–citrullinated protein antibodies (ACPAs) are highly specific for rheumatoid arthritis (RA) and are present years before the onset of symptoms. The avidity of autoantibodies can have a strong impact on their effector potency. This study was undertaken to analyze the avidity of ACPAs in serum samples obtained from ACPA‐positive healthy individuals (predisease), patients with early disease, and patients with established RA as well as the avidity maturation over time in samples from healthy subjects who later developed RA.

We measured ACPA avidity in serum samples from ACPA‐positive healthy individuals, symptomatic individuals, and patients with established RA in 5 collections from The Netherlands, Canada, and Austria. We determined the dynamics of avidity maturation of ACPAs from the predisease stage to established disease in 1 case from the native North American population and in 10 cases from a Dutch blood donor cohort.

The overall ACPA response was characterized by low‐avidity antibodies. Higher‐avidity ACPAs were observed in symptomatic patients only, while low‐avidity ACPAs were observed in both healthy subjects and patients. In longitudinal samples obtained from subjects prior to disease onset, ACPA avidity increased over time until disease onset. No further avidity maturation was observed after disease onset.

Our findings indicate that avidity maturation of the ACPA response takes place prior to disease onset.