Background Rheumatoid arthritis (RA) beginning at older age differs from younger-onset RA by several clinical characteristics. Existing data on the association between age of onset and prevalence of autoantibodies are conflicting. Therefore this study determined this association in five cohorts. Furthermore, the association between age of onset and characteristics of the anti-citrullinated protein antibodies (ACPA)-response was explored.

Materials and methods 3,321 1987-positive RA-patients included in the Leiden-EAC, BARFOT, ESPOIR, Umeå and Lund cohorts were studied on age at diagnosis and presence of ACPA, rheumatoid factor (RF) and anti-carbamylated protein (anti-CarP) antibodies at disease presentation. Logistic regression analyses were performed and effect sizes were summarised in inverse-weighted meta-analyses. ACPA-level was studied within all cohorts and ACPA-isotypes, ACPA-fine-specificity and ACPA-avidity index and clinical characteristics were studied in the Leiden-EAC.

Results From the age of fifty onwards, the proportion of ACPA-positive patients decreased with a higher age of onset (OR 0.96 per 1-year increase in age, 95% CI 0.95–0.97). Similar observations were done for RF and anti-CarP. ACPA-level, number of ACPA-isotypes, ACPA-fine-specificity and avidity in ACPA-positive RA-patients were similar in different age-categories. RA-patients older at disease-onset were less often smokers, had higher acute phase reactants and had more often a (sub)acute onset of symptoms.

Conclusions Characteristics of the ACPA-response in ACPA-positive RA-patients appeared not age-dependent. The proportion of ACPA-negative RA-patients increased with higher age. The associations with clinical features suggest that part of the ACPA-negative RA-patients with onset at higher age have differences in etiopathology. Further biologic studies are needed to promote personalised medicine in RA.