Avidity maturation of ACPA in rheumatoid arthritis

Abstract

OBJECTIVES: Anti-citrullinated protein antibodies (ACPA) are highly specific for rheumatoid arthritis (RA) and are present years before onset of symptoms. Avidity of (auto) antibodies can have a strong impact on their effector potency. Here, we analyzed the avidity of ACPA in pre-disease, early-disease and established RA samples as well as avidity maturation in time in samples of healthy subjects that later developed RA. METHODS: We measured ACPA avidity in samples from ACPA-positive healthy individuals, symptomatic individuals and patients with established RA derived from five collections from The Netherlands, Canada and Austria. Furthermore, we determined the dynamics of avidity maturation of ACPA from the stage of pre-disease to established disease in one case from the native North American population and 10 cases from a Dutch blood donor cohort. RESULTS: The overall ACPA response was characterized by low avidity antibodies. Individuals with higher avidity ACPA were confined to symptomatic patients, while low avidity ACPA were observed in both healthy subjects and patients. In longitudinal samples obtained from subjects prior to disease onset, the ACPA avidity increased over time until disease onset. Following onset of disease no further avidity maturation was observed. CONCLUSIONS: Avidity maturation of the ACPA response takes place prior to disease onset.