The relationship of serum growth differentiating factor 15 with hepcidin in posttransplant adult Egyptian patients and its prognostic significance

IF 0.1 Q4 HEMATOLOGY
M. Elrazzaz, M. Azzazi, Amal M Alafifi, H. Hegab, A. El-Ghammaz, M. Shazly
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Abstract

Background Hepcidin is a small peptide that is produced in the liver that is most likely the major regulator of iron. Based upon the importance of iron, multiple mechanisms exist for the regulation of hepcidin. Iron levels, inflammation, erythropoiesis, and the combined effects of several proteins expressed on hepatocyte membranes are involved. Growth differentiation factor 15 (GDF15) is a member of the transforming growth factor-b. GDF15 expression level is usually low in resting cells but may be substantially increased following response to diverse cellular stress signals, such as hypoxia, inflammation, acute tissue injury, and during cancer progression. Aim The aim was to assess the relationship of serum GDF15 with hepcidin in posttransplant adult Egyptian patients as an assessment for iron overload and their relationship with posttransplantation complications. Patients and methods Serum GDF15 and hepcidin were measured using enzyme-linked immunosorbent assay in 45 postallogenic (23 patients) and autologous (22 patients) bone marrow transplanted patients 1 year after transplantation in comparison with 15 healthy controls recruited from the bone marrow transplantation unit, Ain Shams University Hospitals. Results Serum level of GDF15 and hepcidin level were elevated 1 year after allogenic and autologous transplantation patients in comparison with control group, with a statistically significant difference between patients and controls (P<0.001). GDF15 and hepcidin were positively correlated with ferritin level (P<0.001). GDF15 and ferritin were positively correlated with acute graft-versus-host disease (GVHD) and chronic GVHD (P=0.004 and 0.002, respectively), but hepcidin did not show any significant correlation with acute GVHD (P=0.110). Moreover, GDF15, hepcidin and ferritin were positively correlated with serum levels of alanine transferase and aspartate transferase in both autologous and allogenic transplanted patients. However, GDF15, hepcidin, and ferritin were not correlated with bacterial or viral infections in both allogenic and autologous groups of patients. Conclusion Both GDF15 and hepcidin are useful biomarkers for iron overload in late postallogenic and autologous bone marrow transplantation, and both can be used as a predictor for posttransplantation complications.
埃及成年患者移植后血清生长分化因子15与铁调素的关系及其预后意义
Hepcidin是一种在肝脏中产生的小肽,很可能是铁的主要调节剂。基于铁的重要性,hepcidin的调控存在多种机制。铁水平、炎症、红细胞生成以及肝细胞膜上表达的几种蛋白质的综合作用都涉及其中。生长分化因子15 (Growth differentiation factor 15, GDF15)是转化生长因子b的成员。在静息细胞中,GDF15的表达水平通常较低,但在对各种细胞应激信号(如缺氧、炎症、急性组织损伤和癌症进展)做出反应后,GDF15的表达水平可能大幅增加。目的评估埃及成年移植后患者血清GDF15与hepcidin的关系,以评估铁超载及其与移植后并发症的关系。患者和方法采用酶联免疫吸附法测定45例移植后(23例)和自体(22例)骨髓移植1年后患者的血清GDF15和hepcidin,并与从艾因沙姆斯大学医院骨髓移植部门招募的15例健康对照进行比较。结果同种异体和自体移植患者术后1年血清GDF15水平和hepcidin水平均高于对照组,差异有统计学意义(P<0.001)。GDF15、hepcidin与铁蛋白水平呈正相关(P<0.001)。GDF15和铁蛋白与急性移植物抗宿主病(GVHD)和慢性GVHD呈正相关(P分别为0.004和0.002),而hepcidin与急性GVHD无显著相关性(P=0.110)。此外,GDF15、hepcidin和铁蛋白与自体和同种异体移植患者血清丙氨酸转移酶和天冬氨酸转移酶水平呈正相关。然而,在同种异体和自体患者中,GDF15、hepcidin和铁蛋白与细菌或病毒感染无关。结论GDF15和hepcidin均可作为晚期同种异体和自体骨髓移植后铁超载的生物标志物,并可作为移植后并发症的预测指标。
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