Serum HDGFL2 as a novel biomarker for disease activity in Egyptian patients with rheumatoid arthritis

Abstract Background Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disorder characterized by persistent joint inflammation and tissue damage. The pathogenesis of RA involves complex immune dysregulation, necessitating the identification of reliable biomarkers to assess disease activity and progression. Recently, hepatoma-derived growth factor-like 2 (HDGFL2), a member of the HDGF protein family and an epigenetic regulator, has emerged as a potential biomarker. Objective This study evaluated serum HDGFL2 levels in 40 Egyptian RA patients and 40 matched age and sex healthy controls and investigated its potential role as a biomarker for disease activity. Methods Serum HDGFL2 levels were measured using a commercially available enzyme-linked immunosorbent assay (ELISA). Rheumatoid arthritis was classified according to the 2010 ACR/EULAR classification criteria, and disease activity was assessed using the DAS28-based assessment at the initial evaluation before initiation of RA-related treatment. Statistical analyses were performed using appropriate parametric or non-parametric tests according to data distribution, with Spearman’s rank correlation used for correlation analyses and receiver operating characteristic (ROC) analysis used to assess discriminative performance. Results Serum HDGFL2 levels were significantly higher in rheumatoid arthritis (RA) patients than in healthy controls (787.2 ± 476.3 ng/L vs. 330.0 ± 81.52 ng/L, p < 0.001). HDGFL2 levels were positively correlated with white blood cell count, erythrocyte sedimentation rate (ESR), anti-cyclic citrullinated peptide (anti CCP) and C-reactive protein (CRP). ROC analysis identified an optimal cutoff of > 469.5 ng/L for differentiating RA patients from healthy controls (AUC 0.974, 95% CI 0.925–1.00; sensitivity 95.0%; specificity 100.0%). A cutoff of > 582.43 ng/L was identified for distinguishing active from inactive disease (AUC 0.912, 95% CI 0.802–1.000; sensitivity 70.59%; specificity 100.0%). Conclusion In this study, understanding the role of HDGFL2 in RA could provide novel insights into disease mechanisms and suggests that HDGFL2 is a promising exploratory biomarker for diagnosing RA and monitoring disease activity, potentially enhancing clinical management and therapeutic targeting.