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Immunoassay for human serum erythroferrone

Tomas Ganz, Grace Jung, Arash Naeim, Yelena Ginzburg, Zahra Pakbaz, Patrick B. Walter, Léon Kautz and Elizabeta Nemeth

Key points

  • Human serum erythroferrone shows similar pathophysiologic responses to mouse models.

Abstract

Erythroferrone (ERFE) is a glycoprotein hormone secreted by erythroblasts in response to stimulation by erythropoietin. We previously demonstrated that ERFE mRNA expression and serum protein concentration increase in mice subjected to hemorrhage or erythropoietin therapy, that ERFE acts on hepatocytes to suppress hepcidin, and that the resulting decrease in hepcidin augments iron delivery for intensified erythropoiesis. We also showed that ERFE contributes to pathological hepcidin suppression and iron overload in mice with non-transfused β-thalassemia. We now report the development and technical validation of a rabbit monoclonal antibody-based sandwich immunoassay for human ERFE. We use this assay to show that blood loss or erythropoietin administration increase serum ERFE concentrations in humans, and that patients with both non-transfused and transfused β-thalassemia have very high serum ERFE levels, which decrease after blood transfusion. The assay should be useful for human studies of normal and disordered erythropoiesis and its effect on iron homeostasis.

  • Submitted April 5, 2017.
  • Accepted July 12, 2017.