Immunoassay for human serum erythroferrone

Abstract

Erythroferrone (ERFE) is a glycoprotein hormone secreted by erythroblasts in response to stimulation by erythropoietin (EPO). We previously demonstrated that ERFE messenger RNA expression and serum protein concentration increase in mice subjected to hemorrhage or EPO 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 nontransfused 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 EPO administration increases serum ERFE concentrations in humans, and that patients with both nontransfused 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.

Levels of the erythropoietin-responsive hormone erythroferrone in mice and humans with chronic kidney disease

“…However, the aforementioned study of 59 hemodialysis patients did observe a negative correlation between ERFE and hepcidin 7 . Again, assay differences may have contributed to these discrepant observations.…”

“…However, the study did observe a small ERFE increase (15%-20%) in a subset of 20 hemodialysis patients that received erythropoiesis stimulating agents (continuous erythropoietin receptor activator (CERA) or darbepoetin alfa) at three days post-administration 7 . It should be noted that the ERFE assay used in this study (MyBioSource, San Diego, CA) has different characteristics than the human assay we developed and was not validated in physiological or pathological conditions that would be expected to have elevated ERFE levels such as blood donors or patients with β -thalassemia.…”

Modern iron replacement therapy: clinical and pathophysiological insights

“…In murine models, a hormone named erythroferrone (ERFE) has been identified as the hepcidin suppressing agent produced by erythroblasts [9,31]. In humans, the ERFE ortologue encoded by the gene FAM132B seems also involved in hepcidin suppression under conditions of increased erythropoiesis [32,33], although in combination with other factors still poorly characterized [23]. Finally, inflammation strongly stimulates hepcidin synthesis through several interleukins (IL), mainly IL-6 [34] and IL-1β [35].…”

MRI as an alternative to serum ferritin for diagnosis of iron overload in children in the context of immune response after stem cell transplantation

“…But, a complete recovery was not observed in any patient within the study period. In patients with thalassemia, cellular iron uptake is downregulated through hepcidin after many transfusions . A reduced dietary iron uptake and the physiological iron loss (eg, by exfoliation of intestinal mucosa cells) might therefore still compensate the increasing iron stores, as we are evaluating the iron levels from the start of the transfusion therapy.…”