Serum hepcidin level and erythropoietic activity after hematopoietic stem cell transplantation

Abstract

The relationship between serum hepcidin, a key regulator of body iron homeostasis, and erythropoiesis was investigated before and after stem cell transplantation in 31 patients with hematopoietic malignancies. Serum hepcidin-25 was monitored using a liquid chromatography-tandem mass spectrometry-based assay system. Other iron-and erythropoiesis-related parameters and known hepcidin regulators, such as interleukin-6 and growth differentiation factor-15, were also monitored. The serum hepcidin level peaked one week after stem cell transplantation, followed by a gradual decrease with a parallel change in interleukin-6 and a reciprocal change in reticulocyte count. Multivariate regression analysis demonstrated that the serum hepcidin level at four weeks after stem cell transplantation showed significant inverse correlations with erythropoietic activity markers, such as the soluble transferrin receptor, but not with growth differentiation factor-15. These results indicate the existence of an unknown functional erythropoiesis-associated circulating factor, other than growth differentiation factor-15, that negatively regulates hepcidin production in stem cell transplantation settings.

Serum hepcidin following autologous hematopoietic cell transplantation: an illustration of the interplay of iron status, erythropoiesis and inflammation

“…[4][5][6] We also identified a hepcidin peak one week after transplantation. Whereas Kanda attributed this peak to inflammation because of a concomitant elevation of serum IL-6 levels (not measured in our study), 5 and although CRP in our study also peaked at Day 7 (data not shown), we did not observe any correlation between hepcidin and CRP values.…”

“…Hepcidin is the key regulator of iron metabolism but has been little investigated in the context of HCT. [4][5][6][7] Hepcidin peaked at Day 7 post transplant and then gradually decreased in the following three weeks without returning to pre-transplant levels. 5 In another study, 6 hepcidin levels at 3-5 months post transplant remained unchanged compared to (high) pre-transplant values.…”

“…[4][5][6][7] Hepcidin peaked at Day 7 post transplant and then gradually decreased in the following three weeks without returning to pre-transplant levels. 5 In another study, 6 hepcidin levels at 3-5 months post transplant remained unchanged compared to (high) pre-transplant values. On the other hand, hepcidin response to erythropoietin therapy has been examined in healthy volunteers 10 or chronic kidney disease 10,11 in whom erythropoietin (EPO) elicited a rapid and persistent drop in serum hepcidin levels.…”

New and old players in the hepcidin pathway

“…J. Kanda et al performed an in vivo physiological study of the relationship between serum hepcidin and erythropoiesis in the clinical setting of stem cell transplantation (SCT). 22 They monitored the pre-and post-SCT serum hepcidin levels together with other factors potentially affecting hepcidin expression. Four weeks after SCT, at a time when hepcidin levels are no longer related to the inflammatory cytokine IL-6, they found that serum hepcidin levels show a significant inverse correlation with markers of erythropoietic activity, such as the soluble transferrin receptor and the reticulocyte counts, but not with GDF15 levels.…”

“…Melis et al report a Sardinian inbred family with 5 members affected with IRIDA due to a novel TMPRSS6 mutation, 20 Pagani et al studied the processing of HJV mutants and their ability to activate hepcidin in vitro, 21 while Kanda et al investigated the relationship of hepcidin with markers of erythropoiesis in the stem cell transplantation (SCT) setting. 22 This review summarizes current knowledge of the hepcidin pathway and of the regulation of the hepcidin expression.…”