Peptidylarginine deiminase 4 (PAD4) activity in early rheumatoid arthritis
| Autor: | Katherine Falkowski, Ardita Aliko, Espen A Haavardsholm, Tomasz Kantyka, B.-T.S. Fevang, Anna-Birgitte Aga, M.K. Jonsson, Siri Lillegraven, Piotr Mydel, Joseph O. Sexton |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Adult
Male Arginine Immunology Arthritis Anti-Citrullinated Protein Antibodies Arthritis Rheumatoid chemistry.chemical_compound Protein-Arginine Deiminase Type 4 Rheumatology Rheumatoid Factor Peptidylarginine Deiminase Citrulline Humans Immunology and Allergy Medicine Risk factor Aged business.industry General Medicine Early rheumatoid arthritis Middle Aged medicine.disease chemistry Female business |
| Popis: | 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 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. |
| Databáze: | OpenAIRE |
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