High levels of soluble serum hemojuvelin in patients with congenital dyserythropoietic anemia type I

Objective Congenital dyserythropoietic anemia (CDA) is a rare group of red blood cell disorders with ineffective erythropoiesis and secondary hemochromatosis. Inappropriate suppression of hepcidin and high levels of growth differentiation factor 15 (GDF15) have been described in CDA I and II patients, probably contributing to secondary hemochromatosis. Hemojuvelin (HJV) is an important regulator of serum hepcidin, while soluble form of HJV (s‐HJV) competitively down‐regulates hepcidin. Methods We determined the soluble hemojuvelin (s‐HJV) levels in 17 patients with CDA I and in 17 healthy volunteers (HV) and looked for correlations with other parameters of iron overload and erythropoiesis. Results Significantly higher levels of s‐HJV were found in patients (2.32 ± 1.40 mg/L) compared with healthy volunteers (0. 69 ± 0.44 mg/L) (P = 0.001). Western blot analysis confirmed the presence of high levels of s‐HJV in CDA I patients. s‐HJV positively correlated with serum ferritin, erythropoietin, soluble transferrin receptor, and GDF15 and negatively correlated with hepcidin to ferritin ratios. Conclusions We for the first time documented high levels of serum s‐HJV in CDA I patients, suggesting that it may contribute to iron loading pathology in CDA I and eventually in other anemias with ineffective erythropoiesis.