Hematopoietic cell transplantation (HCT) brings important alterations in erythropoiesis and iron metabolism. Hepcidin, which regulates iron metabolism, increases in iron overload or inflammation and decreases with iron deficiency or activated erythropoiesis. Erythroferrone (ERFE) is the erythroid regulator of hepcidin. We investigated erythropoiesis and iron metabolism after allogeneic HCT in 70 patients randomized between erythropoietin (EPO) treatment or no EPO, by serially measuring hepcidin, ERFE, CRP (inflammation), soluble transferrin receptor (sTfR, erythropoiesis), serum iron and transferrin saturation (Tsat; iron for erythropoiesis) and ferritin (iron stores). We identified biological and clinical factors associated with serum hepcidin and ERFE levels. Serum ERFE correlated overall with sTfR and reticulocytes and inversely with hepcidin. Erythroferrone paralleled sTfR levels, dropping during conditioning and recovering with engraftment. Inversely, hepcidin peaked after conditioning and decreased during engraftment. Erythroferrone and hepcidin were not significantly different with or without EPO. Multivariate analyses showed that the major determinant of ERFE was erythropoiesis (sTfR, reticulocytes or serum Epo). Pretransplant hepcidin was associated with previous RBC transfusions and ferritin. After transplantation, the major determinants of hepcidin were iron status (ferritin at all time points and Tsat at day 56) and erythropoiesis (sTfR or reticulocytes or ERFE), while the impact of inflammation was less clear and clinical parameters had no detectable influence. Hepcidin remained significantly higher in patients with high compared to low pretransplant ferritin. After allogeneic HCT with or without EPO therapy, significant alterations of hepcidin occur between pretransplant and day 180, in correlation with iron status and inversely with erythroid ERFE.

中文翻译：

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异基因造血干细胞移植过程中红细胞生成素和铁调素作为红细胞生成和铁代谢之间的介质

造血细胞移植 (HCT) 带来了红细胞生成和铁代谢的重要改变。调节铁代谢的铁调素会增加铁过载或炎症，并随着铁缺乏或红细胞生成激活而减少。Erythroferrone (ERFE) 是铁调素的红系调节剂。我们通过连续测量铁调素、ERFE、CRP（炎症）、可溶性转铁蛋白受体（sTfR，红细胞生成）、血清铁和转铁蛋白饱和度，研究了 70 名随机接受促红细胞生成素（EPO）治疗或不使用 EPO 的患者异基因 HCT 后的红细胞生成和铁代谢。 Tsat；用于红细胞生成的铁）和铁蛋白（铁储存）。我们确定了与血清铁调素和 ERFE 水平相关的生物学和临床因素。血清 ERFE 总体上与 sTfR 和网织红细胞相关，与铁调素呈负相关。Erythroferrone 与 sTfR 水平平行，在调节期间下降并随着植入而恢复。相反，铁调素在调节后达到峰值，在植入过程中下降。Erythroferrone 和 hepcidin 在有或没有 EPO 的情况下没有显着差异。多变量分析表明，ERFE 的主要决定因素是红细胞生成（sTfR、网织红细胞或血清 Epo）。移植前铁调素与以前的红细胞输血和铁蛋白有关。移植后，铁调素的主要决定因素是铁状态（所有时间点的铁蛋白和第 56 天的 Tsat）和红细胞生成（sTfR 或网织红细胞或 ERFE），而炎症的影响不太清楚，临床参数没有可检测到的影响。与移植前低铁蛋白相比，高铁患者的铁调素仍然显着升高。