FRI0025 Serum mediated peptidylarginine deiminase (PAD) activation in early rheumatoid arthritis

BackgroundPeptidylarginine deiminases (PADs) are a family of enzymes catalysing the conversion of arginine residues to citrulline, a post translational modification which has been recognised in the generation of neo-epitopes due to anti-citrullinated protein antibodies (ACPAs) in rheumatoid arthritis (RA). ACPAs are included in the classification criteria for RA, and may be present before disease onset and predictive of disease progression.ObjectivesTo investigate whether serum of patients with early RA have the capacity to significantly increase the citrullination performed by PAD enzymes, and the possible role of increased enzyme activation as a mechanism preceding the production of ACPAs.MethodsSerum from DMARD-naïve, early RA patients from the ARCTIC trial1 classified according to the 2010 ACR/EULAR criteria were analysed for PAD4 activating capacities using HPLC fluorometric method. A sample was defined as positive if above mean +2 SD of the healthy controls. Patient characteristics and subgroups with PAD activity were assessed using Mann-Whitney U-test and chi-square test as appropriate.ResultsA total of 225 patients and 63 controls were included in the study. Patient characteristics and measures of disease activity and radiographic damage are presented in the table 1. Median PAD activity levels were higher in patients than in healthy controls (8768 [7491,11393] vs. 7046 [6347,7905], p<0.0001; figure 1). ACPA and rheumatoid factor (RF) positive patients had higher PAD activity than ACPA and RF negative patients (9104 [7739,13213] vs. 7281 [6764,9010], p<0.0001, and 8871 [7715,12259] vs. 8407 [6867,10062], p=0.048, respectively). PAD positivity occurred in 42% (n=95) of the patients and was more prevalent in ACPA positive compared to ACPA negative patients (47 vs. 20%, p=0.002), but not in RF positive vs. RF negative patients (44 vs. 38%, p=0.49). Disease Activity Score was numerically higher in patients positive for PAD than patients who were PAD negative (3.6 (1.1) vs. 3.3 (1.2), p=0.08).ConclusionsSerum capacity to activate PAD4 was associated with ACPA and RF positivity in patients with early RA, but no distinct relationship was seen for Disease Activity Score.Reference[1] Haavardsholm, et al. BMJ2016.Disclosure of InterestM. Jonsson: None declared, K. Falkowski: None declared, A. Aliko: None declared, A.-B. Aga: None declared, S. Lillegraven: None declared, J. Sexton: None declared, B.-T. Fevang: None declared, P. Mydel: None declared, E. Haavardsholm Grant/research support from: AbbVie, Pfizer, MSD, UCB, Roche