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Predictive value of hepcidin and HIF1α protein levels for iron deposition in β-thalassemia
1Faculty of Medicine, Macau University of Science and Technology, Macao, China. 3250004963@student.must.edu.mo.
Insights
Lower hepcidin and higher HIF1α levels indicate increased iron deposition in children with β-thalassemia. These factors may serve as biomarkers for assessing iron overload in this patient group.
Area of Science:
- Hematology
- Pediatric Medicine
- Molecular Biology
Background:
- Transfusion-dependent thalassemia necessitates iron chelation therapy due to iron overload.
- Hepcidin and HIF1α are recently identified erythroid factors regulating iron metabolism.
- Existing knowledge suggests hepcidin negatively correlates and HIF1α positively correlates with iron deposition in pediatric β-thalassemia.
Purpose of the Study:
- To investigate differences in hepcidin, HIF1α, HIF2α, and ERFE expression in children with β-thalassemia based on serum ferritin levels.
- To identify potential biomarkers for assessing iron deposition severity in pediatric β-thalassemia.
Main Methods:
- A cohort of 93 children with β-thalassemia was divided into two groups based on serum ferritin (SF) levels (>1000 μg/L and <1000 μg/L).
- Enzyme-linked immunosorbent assay (ELISA) was employed to measure the relative expression levels of hepcidin, HIF1α, HIF2α, and ERFE.
- Statistical analysis, including odds ratio (OR) and area under the curve (AUC), was used to evaluate biomarker potential.
Main Results:
- Lower hepcidin protein levels (OR=0.999, AUC=0.650) and higher HIF1α protein levels (OR=2.352, AUC=0.703) were significantly associated with increased iron deposition.
- Specific cutoff values were determined for hepcidin (1.710 ng/mL) and HIF1α (2.115 ng/mL) with defined sensitivity and specificity.
- These findings indicate an inverse relationship between hepcidin and iron deposition, and a direct relationship between HIF1α and iron deposition in the studied pediatric population.
Conclusions:
- Hepcidin and HIF1α demonstrate promise as biomarkers for evaluating iron deposition in children with β-thalassemia.
- Further research is warranted to explore the therapeutic potential of hepcidin and HIF1α in managing iron overload disorders.
- These biomarkers may aid in assessing iron deposition severity, particularly when confounding factors like inflammation are excluded.
Abstract:
To investigate differences in the relative expression levels of the novel iron regulatory erythroid factors hepcidin, HIF1α, HIF2α, and ERFE in children with β-thalassemia exhibiting different serum ferritin (SF) levels. A total of 93 children with β-thalassemia were enrolled from the First Affiliated Hospital of Guangxi Medical University between October 2022 and May 2023. Participants were categorized based on their SF levels: 64 with SF>1000 μg/L and 29 with SF<1000 μg/L. ELISA assays were used to determine the relative expression levels of hepcidin, HIF1α, HIF2α, and ERFE between the two groups. The odds ratio (OR) for hepcidin protein was 0.999 (p<0.05), with an area under the curve (AUC) of 0.650 (p<0.05). Sensitivity and specificity were 46.9% and 82.8%, respectively, with a cutoff value of 1.710 ng/mL. The OR for HIF1α protein was 2.352 (p<0.05), with an AUC of 0.703 (p<0.05). Sensitivity and specificity were 43.8% and 89.7%, respectively, with a cutoff value of 2.115 ng/mL. Lower hepcidin levels and higher HIF1α levels were associated with an increased likelihood of iron deposition in children with β-thalassemia.
Conclusions:
Hepcidin and HIF1α appear to be promising biomarkers for assessing iron deposition in β-thalassemia. Therefore, it is necessary to further investigate their potential as therapeutic targets for β-thalassemia and other iron deposition related disorders.
What Is Known:
• Patients with transfusion-dependent thalassemia require iron chelation therapy. • Hepcidin and HIF1α are recently identified iron regulatory erythroid factors.
What Is New:
•In children with β-thalassemia, hepcidin protein levels are negatively correlated with iron deposition, whereas HIF1α protein levels are positively correlated. • Hepcidin and HIF1α may serve as novel biomarkers for iron deposition in β-thalassemia, providing potential value in evaluating iron deposition severity when inflammation and infection are excluded.
