Erythroid activity modulates iron regulation in pathological erythropoiesis: A cross-sectional case-control study.

Abstract

Background & objectives Genetic defects and altered synthesis of RBCs characterise β-thalassemia and polycythaemia vera (PV), respectively. In both diseases, stress erythropoiesis leads to accelerated erythroid expansion, although iron regulation has not been well studied. Here, we analysed iron parameters and iron regulatory gene expression in individuals affected with β-thalassemia and PV. Methods Biochemical iron parameters and gene expression analysis were carried out in 20 individuals with transfusion-dependent thalassemia (TDT), 20 individuals with non-transfusion-dependent thalassemia (NTDT), 25 individuals affected with PV, and 50 healthy controls. Results Increased soluble transferring receptor (sTfR) levels in both diseases are evidence of increased erythropoietic activity. Compared to the β-thalassemia intermedia group, affected individuals with β-thalassemia major showed significantly elevated serum ferritin levels, whereas subnormal ferritin levels were observed in the PV group. In TDT, hepcidin levels were relatively low compared to ferritin levels, whereas in PV, the increase in erythropoiesis resulted in reduced hepcidin production. In both thalassemia cohorts, diminished TFRC expression in reticulocytes suggested impaired iron uptake, whereas in PV, increased TFRC and FPN1B expression implied increased iron acquisition in reticulocytes despite reduced iron reserves. Interpretation & conclusions Thus, increased erythropoietic activity has a crucial role in determining the quantity of iron transported to the marrow. This is achieved through the modulation of iron regulation within erythroid cells, ultimately affecting systemic iron levels.