Association of anti-pad4 antibodies with erosion and biological treatment use in rheumatoid arthritis.

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Abstract

Background: Novel biomarkers have been described in rheumatoid arthritis (RA) patients, including antibodies to carbamylated proteins (anti-CarP) and to protein-arginine deiminases (PAD). Anti-PAD4 antibodies are associated with anti-citrullinated protein antibodies (ACPA) and worse baseline radiographic joint damage [1]. A subset of anti-PAD4 antibodies that cross-react with PAD3 and are associated with erosive disease, ACPA and progress despite treatment have also been described [1]. Objectives: To evaluate several novel RA markers in a cohort of RA and controls and their association with erosive disease and biological treatment use in RA. Methods: Sera from 116 RA patients [63 young onset RA (YORA) and 53 elderly onset RA (EORA)] and 155 controls [134 polymyalgia rheumatica (PMR) patients and 21 healthy individuals (HI) older than 60 years old] were included. Information on erosion status and biological treatment was available for 56 of the RA patients. The samples were tested for anti-PAD3 and anti-PAD4 IgG using the novel particle-based multi-analyte technology (PMAT, research use only, RUO), as well as for ACPA [CCP3 IgG ELISA and chemiluminescent immunoassay (CIA)] and anti-CarP IgG (ELISA, RUO). Results: Significantly higher levels of anti-PAD3, anti-PAD4 and ACPA (ELISA and CIA) but not CarP were observed in YORA vs. EORA (p<0.0001 for anti-PAD3 and ACPA ELISA and CIA, p=0.0016 for anti-PAD4). In the RA patients with erosion and treatment information available, anti-PAD4 antibody levels, but not ACPA, anti-CarP or anti-PAD3, were significantly higher in patients on biologic treatment vs. patients that were not on biologics (p=0.0017). Anti-PAD4 positive patients, were 10.1 [95% CI 2.5-52.0, p=0.0002] times more likely to be on biologic treatment vs. the negative group. Similarly, anti-PAD4 antibodies, but neither ACPA nor anti-CarP or anti-PAD3, were also significantly higher in patients with joint erosions (p=0.0354). All patients that were positive for anti-PAD4 antibodies (n=21) had erosive disease. Anti-PAD4 positive patients, were 20.2 [95% CI 1.1-363.2, p=0.0041] times more likely to have erosive disease.