Peptidylarginine deiminase 4 (PAD4) activity in early rheumatoid arthritis. (3rd March 2020)

• Record Type: Journal Article
• Authors: Jonsson, MK; Kantyka, T; Falkowski, K; Aliko, A; Aga, AB; Lillegraven, S; Sexton, J; Fevang, BT; Mydel, P; Haavardsholm, EA
• Is Part Of: Scandinavian journal of rheumatology. Volume 49:Number 2(2020)
• Page Start: 87
• Page End: 95
• Publication Date: 2020-03-03
• Subjects: Rheumatology -- Periodicals; Arthritis; Rheumatic Diseases; 616.72005
• DOI: 10.1080/03009742.2019.1641216
• Languages: English
• ISSNs: 0300-9742

Abstract

Abstract : Objectives : 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 (PADAct ) in early RA, and the associations between PAD activation and disease characteristics, treatment response, and progression of radiographic damage. Method : 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 PADAct were evaluated by Mann–Whitney U and chi-squared tests. Changes in PADAct levels were compared using the Wilcoxon signed-rank test. Results : PADAct 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). PADAct -positive were younger than PADAct -negative patients [mean ± sd 48.7 ± 13.5 vs 53.2 ± 13.7 years, p = 0.011]. Median [25th, 75th percentile] PADAct 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. Conclusion : 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.