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

Abstract

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease manifested by persistent synovial inflammation and progressive destruction of joints. 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. 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. 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). 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.