The impact of the presence of autoantibodies against citrullinated, carbamylated and acetylated peptides on radiographic progression in patients with new onset rheumatoid arthritis: an observational study

Background A range of anti-modified peptide autoantibodies (AMPA) are associated with rheumatoid arthritis (RA). We assessed the relationship between AMPA profiles and radiographic progression in new onset RA. Methods AMPAs (targeting citrullinated, carbamylated and acetylated peptides) were measured by ELISA in 362 patients with new onset RA from the Scottish Early Rheumatoid Arthritis Inception Cohort and Biobank (SERA). Radiographic progression in hands and feet was determined using the Sharp-van der Heijde (SvH) method. 233 patients with RA had AMPA status and radiographic progression scores after quality control. Differences in radiographic progression between groups were determined using least square means changes with baseline value of radiographic variable, rheumatoid factor, gender, age of onset of disease, symptom duration and baseline DAS28-CRP included as covariates. Findings Four main autoantibody groupings by class of modification were identified in RA patients (n=362) with reactivities against modified peptides as follows: citrullinated only (n=73, 20%), citrullinated and acetylated (n=45, 12%), citrullinated, carbamylated and acetylated (n=151, 42%) and AMPA negative (n=74, 20%). In RA patients with both antibody and radiographic data, those with antibodies against all three post-translational modifications (least square mean 1·7, n=97) had greater radiographic progression over 12 months compared to those with anti-citrullinated peptide antibodies (ACPA) only (least square mean 0·5, n=48) (least square mean difference of total SvH score of 1·2, 95% CI 0·05-2.40). There was no difference in progression comparing ACPA only with seronegative patients (least square mean 0.7, n=47) (least square mean difference -0.2, 95% CI -1·09-0·67). Interpretation RA patients with all three classes of AMPA have more rapid radiographic progression over 12 months than those with ACPA alone. Patients with ACPA alone had similar radiographic progression over 12 months to AMPA negative patients.