Erythropoiesis lagging? pIgA1 steps in to assist Epo

Abstract

Although erythropoietin (Epo) is commonly used as a therapy for anemia, recent studies have suggested that Epo therapy is associated with adverse outcomes. A new study shows that polymeric IgA1 positively regulates erythropoiesis through binding to transferrin receptor 1 (Tfr1), suggesting new therapeutic routes for anemia (pages 1456–1465).

Figure 1

pIgA1 and Fe-Tf bind TfR1 to stimulate Epo-dependent erythroblast proliferation and development. Coulon et al. present a new model of erythropoiesis, which might allow the development of new therapeutic approaches for anemia and other disorders associated with dyserythropoiesis. Under steady-state conditions (left), low concentrations of pIgA1 are produced by plasma cells, and most TfR1 is bound by Fe-Tf, with little stimulation of downstream ERK and Akt signaling pathways. Stress conditions such as hypoxia can lead to increased pIgA1 production, allowing erythroid development to be boosted via ERK and Akt signaling. The role of pIgA1 becomes more important in iron deficiency anemia, where Tf saturation is low, limiting the ability of Fe-Tf to stimulate erythropoiesis.