Interplay of erythropoietin, fibroblast growth factor 23, and erythroferrone in patients with hereditary hemolytic anemia.

Abstract

Recently, erythropoietin (EPO) was identified as regulator of fibroblast growth factor 23 (FGF23). Proteolytic cleavage of biologically active intact FGF23 (iFGF23) results in the formation of C-terminal fragments (cFGF23). An increase in cFGF23 relative to iFGF23 suppresses FGF receptor signaling by competitive inhibition. EPO lowers the i:cFGF23 ratio, thereby overcoming iFGF23-mediated suppression of erythropoiesis. We investigated EPO-FGF23 signaling and levels of erythroferrone (ERFE) in 90 patients with hereditary hemolytic anemia (www.trialregister.nl [NL5189]). We show, for the first time, the importance of EPO-FGF23 signaling in hereditary hemolytic anemia: there was a clear correlation between total FGF23 and EPO levels (r = +0.64; 95% confidence interval [CI], 0.09-0.89), which persisted after adjustment for iron load, inflammation, and kidney function. There was no correlation between iFGF23 and EPO. Data are consistent with a low i:cFGF23 ratio. Therefore, as expected, we report a correlation between EPO and ERFE in a diverse set of hereditary hemolytic anemias (r = +0.47; 95% CI, 0.14-0.69). There was no association between ERFE and total FGF23 or iFGF23, which suggests that ERFE does not contribute to the connection between FGF23 and EPO. These findings open a new area of research and might provide potentially new druggable targets with the opportunity to ameliorate ineffective erythropoiesis and the development of disease complications in hereditary hemolytic anemias.

• Authors: Annelies J van Vuren, Michele F Eisenga, Stephanie van Straaten, Andreas Glenthøj, Carlo A J M Gaillard, Stephan J L Bakker, Martin H de Borst, Richard van Wijk, Eduard J van Beers
• Journal: Blood advances (Blood Adv) Vol. 4 Issue 8 Pg. 1678-1682 (04 28 2020) ISSN: 2473-9537 [Electronic] United States
• PMID: 32324886 (Publication Type: Journal Article)
• Copyright: © 2020 by The American Society of Hematology.

Chemical References

• EPO protein, human
• Erfe protein, human
• FGF23 protein, human
• Peptide Hormones
• Erythropoietin
• Fibroblast Growth Factors
• Fibroblast Growth Factor-23
• Iron

Topics

• Anemia, Hemolytic, Congenital
• Erythropoietin
• Fibroblast Growth Factor-23
• Fibroblast Growth Factors
• Humans
• Iron
• Peptide Hormones