Pediatric Department, Faculty of Medicine, Cairo University, Cairo, Egypt.
Clinical Pathology Department, Faculty of Medicine, Cairo University, Cairo, Egypt.
Pediatr Res. 2024 Mar;95(4):1095-1100. doi: 10.1038/s41390-023-02729-5. Epub 2023 Jul 18.
Iron overload can result in grave consequences in thalassemic patients, despite the availability of iron chelators. Therefore, alternative pathways aiming to reduce iron toxicity are currently investigated. Among which, reduction of iron absorption through control of hepcidin production appears to be promising. In this study, we investigated growth differentiation factor-15 (GDF15) and erythroferrone (ERFE) as potential suppressors of hepcidin.
This cross-sectional study was conducted on 61 thalassemic patients and 60 healthy controls. The frequency of GDF15 gene polymorphism (rs4808793) (-3148C/G), serum level of GDF15 and erythroferrone were measured and correlated with those of hepcidin and serum ferritin.
The presence of GDF15 gene mutations were significantly higher in the patients' group compared to controls (P value 0.035). Also, thalassemia patients had significantly higher levels of GDF15 and ERFE and lower hepcidin levels than controls (P value < 0.001). Serum hepcidin level showed significantly negative correlations with GDF15, ERFE, reticulocyte count, LDH level, and serum ferritin. Contrarily, it had highly significant positive correlation with hemoglobin.
High level of GDF15 and/or ERFE may inhibit hepcidin production and increase iron load in patients with thalassemia; therefore, medications that suppress their actions may provide new therapeutic potentials for iron toxicity.
Iron overload continues to be a major contributor to high morbidity and mortality in patients with thalassemia. New strategies together with proper chelation, need to be developed to minimize the effect of iron toxicity. Growth differentiation factor-15 (GDF15) and erythroferrone (ERFE) inhibit hepcidin production and increase iron levels in conditions with ineffective erythropoiesis. Medications that suppress the production or interfere with the action of GDF15 or ERFE may represent new therapeutic potentials for iron toxicity. Prevention of iron toxicity will significantly reduce morbidity and mortality and improve the quality of life of thalassemia patients.
尽管有铁螯合剂可用，但铁过载会导致地中海贫血患者出现严重后果。因此，目前正在研究旨在降低铁毒性的替代途径。其中，通过控制铁调素的产生来减少铁吸收似乎很有前景。在这项研究中，我们研究了生长分化因子 15（GDF15）和红细胞生成素（ERFE）作为铁调素潜在抑制剂的作用。
这项横断面研究共纳入 61 例地中海贫血患者和 60 名健康对照者。测量了 GDF15 基因多态性（rs4808793）（-3148C/G）、血清 GDF15 和红细胞生成素的频率，并与铁调素和血清铁蛋白进行了相关性分析。
与对照组相比，患者组 GDF15 基因突变的发生率明显更高（P 值 0.035）。此外，地中海贫血患者的 GDF15 和 ERFE 水平明显高于对照组，而铁调素水平明显低于对照组（P 值均<0.001）。血清铁调素水平与 GDF15、ERFE、网织红细胞计数、乳酸脱氢酶水平和血清铁蛋白呈显著负相关，而与血红蛋白呈显著正相关。
高水平的 GDF15 和/或 ERFE 可能会抑制铁调素的产生并增加地中海贫血患者的铁负荷；因此，抑制其作用的药物可能为铁毒性提供新的治疗潜力。
铁过载仍是导致地中海贫血患者高发病率和死亡率的主要原因。需要开发新的策略和适当的螯合作用，以尽量减少铁毒性的影响。生长分化因子 15（GDF15）和红细胞生成素（ERFE）在无效红细胞生成的情况下抑制铁调素的产生并增加铁水平。抑制 GDF15 或 ERFE 的产生或干扰其作用的药物可能为铁毒性提供新的治疗潜力。预防铁毒性将显著降低地中海贫血患者的发病率和死亡率，提高生活质量。
