Integrated assessment of the erythroferrone-hepcidin axis, growth differentiation factor-15, and oxidative DNA damage in β-thalassemia patients
College of pharmacy, Ninevah University, Iraq.
Research Article
International Journal of Chemical and Pharmaceutical Research Updates, 2026, 07(01), 061–071.
Article DOI: 10.53430/ijcpru.2026.7.1.0045
Publication history:
Received on 14 June 2026; revised on 20 July 2026; accepted on 22 July 2026
Abstract:
Objective: This study aimed to characterize the integrated pattern of ineffective erythropoiesis, hepcidin regulation, transfusional iron loading, and oxidative DNA damage in patients with β-thalassemia and to explore the ability of the investigated serum biomarkers to classify ferritin-defined severe iron overload.
Methods: This cross-sectional comparative study included 110 consecutively recruited participants at the Al-Hadbaa Specialist Hospital for Blood Diseases and Bone Marrow Transplantation: 45 patients with transfusion-dependent β-thalassemia (TDT), 30 with non-transfusion-dependent β-thalassemia (NTDT), and 35 healthy controls. Serum erythroferrone (ERFE), hepcidin-25, growth differentiation factor-15 (GDF-15), and 8-hydroxy-2′-deoxyguanosine (8-OHdG) were measured by enzyme-linked immunosorbent assays. Hematological variables, iron indices, liver enzymes, bilirubin, scaled ERFE/hepcidin and hepcidin/ferritin indices, correlations, exploratory multivariable models, and receiver operating characteristic (ROC) analyses for a ferritin-defined outcome were evaluated.
Results: TDT patients had the highest ferritin [4016.5 (2500.8-5500.0) ng/mL] and 8-OHdG [350.0 (300.0-400.0) pg/mL]. ERFE and GDF-15 were markedly elevated in both TDT and NTDT, whereas hepcidin was lowest in NTDT [6.5 (5.5-8.0) ng/mL] and remained lower in TDT [7.7 (6.0-9.5) ng/mL] than in controls [25.3 (22.7-27.6) ng/mL]. 8-OHdG correlated positively with ferritin (rs = 0.650, p < 0.001) and alanine aminotransferase (rs = 0.631, p < 0.001). ERFE was independently associated with lower hepcidin (B = -0.015, p < 0.001). Among the evaluated biomarkers, 8-OHdG had the numerically highest AUC for the ferritin-defined outcome (AUC = 0.820, 95% CI 0.720-0.920).
Conclusion: The biomarker profile distinguishes the erythroid-hepcidin disturbance from transfusional iron loading and oxidative DNA injury. The ERFE-hepcidin axis and 8-OHdG may provide complementary mechanistic information alongside ferritin; however, validation against MRI-derived liver and cardiac iron measurements is required before clinical thresholds or diagnostic applications can be established.
Keywords:
β-Thalassemia; Erythroferrone; Hepcidin; GDF-15; 8-OHdG; Iron overload.
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