Jonsson, MK Kantyka, T Falkowski, K Aliko, A Aga, AB Lillegraven, S Sexton, J Fevang, BT Mydel, P Haavardsholm, EA Peptidylarginine deiminase 4 (PAD4) activity in early rheumatoid arthritis <p><b>Objectives</b>: Peptidylarginine deiminases (PADs) are a family of calcium-dependent enzymes catalysing the conversion of arginine residues to citrulline, which may constitute a risk factor in rheumatoid arthritis (RA) pathogenesis. We investigated PAD activation by serum (PAD<sub>Act</sub>) in early RA, and the associations between PAD activation and disease characteristics, treatment response, and progression of radiographic damage.</p> <p><b>Method</b>: Sera from disease-modifying anti-rheumatic drug (DMARD)-naïve early RA patients (n = 225), classified according to the 2010 American College of Rheumatology/European League Against Rheumatism criteria, and healthy controls (n = 63) were analysed for PAD4 activating capacity at 0, 3, 12, and 24 months using a high-performance liquid chromatography fluorometric method. Associations for PAD<sub>Act</sub> were evaluated by Mann–Whitney U and chi-squared tests. Changes in PAD<sub>Act</sub> levels were compared using the Wilcoxon signed-rank test.</p> <p><b>Results</b>: PAD<sub>Act</sub> positivity occurred in 42% (n = 95) of the patients and was more prevalent in anti-citrullinated protein antibody (ACPA)-positive vs ACPA-negative patients (47% vs 20%, p = 0.002), but not in rheumatoid factor (RF)-positive vs RF-negative patients (44% vs 38%, p = 0.49). PAD<sub>Act</sub>-positive were younger than PAD<sub>Act</sub>-negative patients [mean ± sd 48.7 ± 13.5 vs 53.2 ± 13.7 years, p = 0.011]. Median [25th, 75th percentile] PAD<sub>Act</sub> levels were higher in patients than in controls (8768 [7491, 11 393] vs 7046 [6347, 7906], p < 0.0001) and decreased after initiation of DMARD treatment, but were not associated with treatment response or progression of radiographic damage after 2 years of follow-up.</p> <p><b>Conclusion</b>: Serum capacity to activate PAD4 was associated with ACPA and RF positivity and earlier disease onset in early RA patients, and decreased after initiation of DMARD treatment, indicating that anti-PAD treatment could potentially be beneficial in RA.</p> PAD Act positivity;Wilcoxon signed-rank test;radiographic damage;Peptidylarginine deiminase 4;anti-citrullinated protein antibody;treatment response;calcium-dependent enzymes catalysing;disease-modifying anti-rheumatic drug;chromatography fluorometric method;PAD activation;RA patients;DMARD treatment;RF;2010 American College;ACPA;vs;PAD Act levels;PAD 4;PAD Act 2019-09-23
    https://tandf.figshare.com/articles/journal_contribution/Peptidylarginine_deiminase_4_PAD4_activity_in_early_rheumatoid_arthritis/9891551
10.6084/m9.figshare.9891551.v1