PF507 THE HEPCIDIN‐ERYTHROFERRONE AXIS AND ITS RELATIONSHIP WITH ERYTHROPOIESIS IN DIFFERENT TYPES OF ANEMIA
Authors: Del Orbe Barreto R. , Arrizabalaga Amuchastegui B. , María Jose M.J. , María Isabel M.C. , Maite M.G. , Salvador P.P. , Sandra G.R. , Pilar R.A. M. , Ana V.M. 
Published: June 2019

Background:

The regulation of iron stores depends on hepcidin, while the adaptation mechanisms of iron availability in case of anemia are mediated by an erythroid factor that could be erythroferrone (ERFE). ERFE is produced by erythroid precursors in the bone marrow and the spleen in response to erythropoietin (EPO) stimulation and bleeding in animal models. ERFE induces hepcidin suppression during increased erythropoietic activity and thereby increases iron availability for new erythrocytes synthesis. Therefore, a negative correlation between serum ERFE concentrations and Hb level and serum ferritin were observed in pediatric patients with iron deficiency anemia (IDA). The role of so‐called hepcidin‐ERFE axis have not been confirmed in cases of increased and sustained erythropoiesis, like congenital hemolytic or dyserythropoietic anemias.

Aims:

To evaluate hepcidin and ERFE levels in different erythroid disorders to investigate their possible implications on iron metabolism.

Methods:

Multicentric study, in which 5 groups of patients were included: 1) healthy controls, 2) IDA, 3) congenital hemolytic anemias with biochemical data of active hemolysis, 4) congenital anemias with ineffective erythropoiesis (non‐transfusion dependent thalassemia, dyserythropoietic anemia) and 5) hereditary spherocytosis (HS) previously treated with splenectomy. In all groups, determination of hemoglobin, ferritin, hepcidin and ERFE levels was performed. The quantitative measurement of hepcidin in serum was a solid phase enzyme‐linked immunosorbent assay based on the principle of competitive binding, with a detection range 0.153–81 ng/ml and sensitivity 0.153 ng/ml. The quantitative measurement of ERFE (FAM132B) in serum was based on a standard sandwich enzyme‐linked immunosorbent assay technology with a detection range 156–10,000 pg/ml and sensitivity 75 pg/ml.

Results:

A total of 94 patients were included, of which 33 were excluded (distributed in all groups) because they did not have a valid ERFE value (not detectable with the method used). The 61 remaining cases distributed as follows: Healthy controls 26 (42.6%), IDA 9 (14.8%), congenital hemolytic anemia 13 (21.3%), ineffective erythropoiesis 4 (6.5%), splenectomized HS patients 9 (14.8%). The median values of Hb, ferritin, hepcidin and ERFE of the different groups are summarized in table 1.

Summary/Conclusion:

In IDA patients, a statistically significant decrease in hepcidin is observed; otherwise, there is an increase in ERFE, although not statistically significant, that could be explained by the low number of samples analyzed. In hemolytic anemias, despite an increase in erythropoiesis, there is no increase in ERFE, which may be in relation to the absence of anemia (compensated hemolytic anemia) and the increase of hepcidine could be explained by the high ferritin levels. In the ineffective erythropoiesis group, despite the anemia, no statistically significant ERFE‐hepcidin levels were observed. In splenectomized HS patients, ERFE/hepcidine levels were similar to those of the control group.

image

The newly identified ERFE hormone may act as physiological hepcidin suppressor in cases with IDA, but we have to establish this relationship in other types of anemia, for which it is necessary to evaluate more patients. The high number of patients that we had to exclude due to ERFE results outside the assay sensitivity range implies the need of validation and standardization of the method.