Hepcidin Production in Ineffective Erythropoiesis and Chronic Hemolysis: Insights on the Crosstalk Between Erythropoiesis and Iron Metabolism

• Published in: Blood 2011-11, Vol.118 (21), p.346-346
• Main Authors: Fertrin, Kleber Yotsumoto, Lanaro, Carolina, Franco-Penteado, Carla Fernanda, Albuquerque, Dulcinéia Martins, Mello, Mariana Rezende Bandeira, Bezerra, Marcos André Cavalcanti, Domingues, Betania Lucena Borges Tavares, Olbina, Gordana, Saad, Sara T. Olalla, Araujo, Aderson S, Westerman, Mark, Costa, Fernando Ferreira
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V118.21.346.346

Abstract 346 Ineffective erythropoiesis in thalassemias and congenital dyserythropoietic anemia has been associated with hepcidin deficiency and spontaneous iron overload, potentially mediated by an abnormally high production of GDF-15, a cytokine overexpressed by maturing erythroblasts (Tanno et al. Nat Med 2007;13:1096–101; Tamary et al., Blood 2008; 112:5241–5244). In this study, we focused on analyzing hepcidin levels in different disorders affecting red cell production. Twenty patients with transfusion independent β-thalassemia intermedia (TI) were enrolled as a model of hemoglobinopathy with ineffective erythropoiesis, and were compared to 53 patients with sickle cell anemia (SCA), in which erythropoiesis is effective. Seventeen healthy volunteers and 13 patients with other anemic states with chronic hemolysis (hereditary spherocytosis, autoimmune hemolytic anemia, pyrimidine 5’-nucleotidase deficiency) were recruited for comparison. Fourteen patients with megaloblastic anemia due to cobalamin deficiency were studied before, during and after treatment as an alternative model of ineffective erythropoiesis. We have determined hepcidin levels as previously described (Ganz et al. Blood 2008;112:4292–4297), as well as serum ferritin, transferrin saturation (TS) and GDF-15 in all groups. Levels of C reactive protein (CRP) and IL-6, an inducer of hepcidin production, were also determined in controls, SCA and TI. IL-6 levels in SCA patients were increased [mean± standard error of mean (1.69±0.22pg/ml, p=0.047)] when compared to TI (1.33±0.21pg/ml) and controls (0.77±0.18pg/ml), and although there was a positive correlation between IL-6 and hepcidin levels (rS=0.25, p=0.039) this did not correspond to an absolute increase in hepcidin in this group. Indeed, circulating hepcidin levels were lower both in TI (56.24±12.14ng/ml) and SCA patients (52.53±10.97ng/ml) than in controls and other hemolytic anemias (80.23±14.3ng/ml and 120.7±12.2ng/ml, respectively, p=0.013), and did not correlate with the elevated levels of GDF-15 found in the 3 groups of patients (p>0.05). Ferritin levels correlated with both hepcidin and GDF-15 levels (rS=0.38, p=0.0005, and rS=0.63, p