DECREASED BAND-3 ANION TRANSPORT ACTIVITY AND BAND-3 CLUSTERIZATION IN CONGENITAL DYSERYTHROPOIETIC ANEMIA TYPE-II

Congenital dyserythropoietic anemia type II (CDA-II) is the most commo n form of inherited dyserythropoiesis. Erythroid precursor and red blo od cells (RBCs) show characteristic morphological abnormalities. Bioch emical studies have shown that this disease is associated with reduced glycosylation activity, which endows band 3 (anion transporter) with peculiar characteristics. The life span of RBCs may be shortened in pa tients with CDA-II, a phenomenon that has been ascribed to this membra ne defect. We analyzed seven unrelated patients with CDA-II and five c ontrol subjects. In all of the CDA-II patients, erythrocytes presented a band 3 that was thinner than usual and also migrated slightly faste r on SDS-PAGE. Analysis of anion transport function in CDA-II RBC samp les demonstrated decreased anion exchange activity per band 3 molecule . Furthermore, we observed that the CDA-II RBCs contained larger amoun ts of aggregate band 3 than control erythrocytes. Aggregate band 3 has been reported to bind naturally occurring antibodies that mediate the phagocytic removal of RBCs. We provide evidence that both the phagocy tic index (RBCs/macrophage) and the amount of membrane-bound immunoglo bulin (IgG) are elevated in CDA-II erythrocytes. Our results suggest t hat the mild hemolysis observed in patients with CDA-II may be ascribe d to clusterization of band 3, which leads to IgG binding and phagocyt osis, and not to a secondary modification of the cytoskeletal structur e of RBCs.