Diagnostic Utility of Serum Pyrin as a Novel Biomarker in Rheumatoid Arthritis

Background: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease manifested by persistent synovial inflammation and progressive destruction of joints. Objective: To evaluate the diagnostic utility of serum pyrin levels for RA and its diagnostic performance in comparison with established biomarkers such as anti-cyclic citrullinated peptide (anti-CCP) antibodies. Pyrin (also known as marenostrin) is encoded by the Mediterranean fever gene and functions as a pattern recognition receptor that assembles the pyrin inflammasome. Methods: A cross-sectional comparative study was conducted with 120 participants, comprising 60 patients with RA (diagnosed according to the 2010 American College of Rheumatology/European League Against Rheumatism classification criteria, with disease activity assessed by Disease Activity Score 28-erythrocyte sedimentation rate [DAS28-ESR]) and 60 age-matched healthy controls (HC). Serum pyrin and anti-CCP levels were measured using enzyme-linked immunosorbent assay. Results: Serum pyrin levels were significantly higher in patients with RA than in controls (1,138 ± 246 ng/mL vs. 537.4 ± 239 ng/mL; P < .0001). ROC analysis demonstrated that pyrin exhibited strong diagnostic accuracy, with an area under the curve (AUC) of 0.93 (95% CI: 0.87–0.97). At an optimal cutoff of >991.7 ng/mL, pyrin achieved a sensitivity of 78% and specificity of 100%. Anti-CCP ( P < .001) and ESR ( P < .0001) levels were also significantly elevated in the patient group. ROC analysis revealed that anti-CCP exhibited the highest diagnostic accuracy (AUC = 1.00; 95% CI: 1.00–1.00; sensitivity 100%, specificity 100% at cutoff >6.5 U/mL), followed by ESR (AUC = 0.98; 95% CI: 0.95–1.00; sensitivity 95%, specificity 100% at cutoff >20 mm/hr) and pyrin (AUC = 0.93; 95% CI: 0.87–0.97). The mean DAS28-ESR score in RA patients was 4.82 ± 1.34, indicating moderate to high disease activity. Pyrin levels showed a strong positive correlation with DAS28-ESR ( r = 0.72, P < .0001). Conclusion: These findings suggest that serum pyrin demonstrates promising diagnostic accuracy for distinguishing RA patients from healthy individuals. Although anti-CCP and ESR demonstrated superior AUC values in this healthy-control comparison, pyrin uniquely correlated with disease activity (DAS28-ESR), suggesting a complementary role as a disease activity-reflective biomarker rather than a purely diagnostic marker. However, as the present study compared RA patients only with HC, further validation in larger cohorts including disease-control groups (e.g., osteoarthritis, gout, psoriatic arthritis) is essential before routine clinical application can be recommended.