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
| Autor: | Kleber Yotsumoto Fertrin, Betania Lucena Domingues Hatzlhofer, Aderson S Araujo, Dulcineia M. Albuquerque, Sara Terezinha Olalla Saad, Marcos André Cavalcanti Bezerra, Carolina Lanaro, Carla F. Franco-Penteado, Flavia Rubia Pallis, Mark Westerman, Mariana R. B. Mello, Fernando Ferreira Costa, Gordana Olbina |
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| Rok vydání: | 2014 |
| Předmět: |
Ineffective erythropoiesis
medicine.medical_specialty biology Anemia nutritional and metabolic diseases Hematology Iron deficiency medicine.disease_cause medicine.disease Endocrinology Erythropoietin Hepcidin hemic and lymphatic diseases Internal medicine embryonic structures Immunology medicine biology.protein Erythropoiesis GDF15 Soluble transferrin receptor medicine.drug |
| Zdroj: | American Journal of Hematology. 89:385-390 |
| ISSN: | 0361-8609 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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