Background/Purpose: Anti-acetylated-peptide antibodies (AAPA) have recently been described in rheumatoid arthritis (RA) patients and may be used as a further diagnostic marker in patients with  early  arthritis. In this study we aimed to determine the prevalence of AAPA in a cohort of RA patients starting their first conventional synthetic DMARD treatment (csDMARD) and additionally evaluated the usefulness of AAPA as potential predictors of clinical response to methotrexate (MTX) therapy.

Methods: We measured IgG and IgA AAPA by ELISA using two acetylated peptides derived from vimentin. We tested by regression, parametric and non-parametric analyses of disease activity measures if AAPA show potency for predicting response to MTX.  

Results: IgG and/or IgA AAPA were detected in 74.5% of the 110 RA patients who stated MTX treatment:  49% were positive for either IgA or IgG antibodies and 25.5% were IgA/IgG double positive. In the AAPA positive patients, 73.6% were positive for IgG AAPA while 26.4% showed IgA antibodies. Importantly, of the 36.4% of patients negative for both RF and ACPA (double negative), 55% were positive for IgG and/or IgA AAPA, and the remaining patients (i.e. 16% of the total cohort) were completely seronegative (triple-negative), see Table. When comparing triple negative patients with the AAPA positive double-negative ones, no significant difference in baseline characteristics was found but a trend that patients with more seroreactivities showed higher composite disease activity scores. Analyzing the clinical response to MTX, IgG-AAPA positive double-negative patients showed a significantly greater relative SDAI change after 6 months compared to triple-negative patients (p=0.028; median (IQR): -44.6% (-58.5 – -28.90) vs. 5.26% (-23.9 – 55.5%) (Figure). In addition, there was a significantly greater relative change in CRP (p=0.035) and erythrocyte sedimentation rate (p=0.003) in AAPA positive double-negative patients . Table: Crosstable of status of RF, ACPA and antiacetylated peptide antibodies

Figure: Boxplots of relative changes of simplified disease activity score (SDAI) in RF and ACPA negative patients, shown for anti-acetylated (AAPA) positive and negative patients

Conclusion:  AAPA commonly occur in RA patients . Measuring AAPA in addition to RF and ACPA reduced the prevalence of seronegative patients by more than 50 %. These AAPA positive but RF and ACPA negative patients responded significantly better to MTX. Therefore, AAPA positivity in RF and ACPA negative patients identifies a subgroup of patients with a more favorable response to MTX.