Erythropoiesis-driven regulation of hepcidin in human red cell disorders is better reflected through concentrations of soluble transferrin receptor rather than growth differentiation factor 15

Am J Hematol. 2014 Apr;89(4):385-90. doi: 10.1002/ajh.23649.


Growth differentiation factor 15 (GDF-15) is a bone marrow-derived cytokine whose ability to suppress iron regulator hepcidin in vitro and increased concentrations found in patients with ineffective erythropoiesis (IE)suggest that hepcidin deficiency mediated by GDF-15 may be the pathophysiological explanation for nontransfusional iron overload. We aimed to compare GDF-15 production in anemic states with different types of erythropoietic dysfunction. Complete blood counts, biochemical markers of iron status, plasma hepcidin, GDF-15, and known hepcidin regulators [interleukin-6 and erythropoietin (EPO)] were measured in 87 patients with red cell disorders comprising IE and hemolytic states: thalassemia, sickle cell anemia, and cobalamin deficiency. Healthy volunteers were also evaluated for comparison. Neither overall increased EPO,nor variable GDF-15 concentrations correlated with circulating hepcidin concentrations (P = 0.265 and P = 0.872). Relative hepcidin deficiency was found in disorders presenting with concurrent elevation of GDF-15 and soluble transferrin receptor (sTfR), a biomarker of erythropoiesis, and sTfR had the strongest correlation with hepcidin (r(s) = 0.584, P < 0.0001). Our data show that high concentrations of GDF-15 in vivo are not necessarily associated with pathological hepcidin reduction, and hepcidin deficiency was only found when associated with sTfR overproduction. sTfR elevation may be a necessary common denominator of erythropoiesis-driven mechanisms to favor iron absorption in anemic states and appears a suitable target for investigative approaches to iron disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anemia, Iron-Deficiency / blood
  • Case-Control Studies
  • Erythrocytes / metabolism*
  • Erythropoiesis
  • Female
  • Growth Differentiation Factor 15 / blood*
  • Hematologic Diseases / blood*
  • Hepcidins / blood*
  • Humans
  • Iron / blood
  • Iron / deficiency
  • Iron / metabolism
  • Iron Overload / blood
  • Male
  • Receptors, Transferrin / blood*
  • Transferrin / metabolism*


  • GDF15 protein, human
  • Growth Differentiation Factor 15
  • Hepcidins
  • Receptors, Transferrin
  • Transferrin
  • Iron