The erythrocyte effects of haemoglobin O-ARAB

To test the hypothesis that HbO(ARAB) induces an increase in red tell mean corpuscular haemoglobin concentration (MCHC), we studied members of four Tu nisian families who Were either homo- or heterozygous for HbO(ARAB) or were double heterozygotes for HbS and HbO(ARAB). The alpha-gene status was also tested. The findings included: (1) Distinctive variation in red cell densi ty (MCHC) as determined by separation of red cells on isopycnic gradients: (a) All red cells from patients homozygous for HbO(ARAB) were denser than n ormal red cells, as is observed for homozygous HbC patients. (b) In patient s heterozygous for HbO(ARAB) red cell density was strongly influenced by th e presence of alpha-thalassaemia. The coexistence of -alpha/alpha alpha res ulted in an average red cell density slightly greater than normal (AA) red cells. Patients heterozygous for HbOARAB With a normal complement of four a lpha genes had denser red cells similar to sickle cell disease with some ce lls of normal density but with most cells very dense, (c) Finally, the doub le heterozygotes for HbS and HbO(ARAB) had significant haemolytic anaemia a nd red cells denser than normal with some as dense as the densest cells fou nd in sickle cell anaemia. (2) Reticulocytes in patients homozygous for HbO (ARAB) were found in the densest density fraction of whole blood. (3) Catio n transport in patients homozygous for HbO(ARAB) was abnormal, with K:Cl co transport activity similar to that of HbS-Oman and only somewhat lower than in sickle fell anaemia red cells. The activity of the Gardos channel was i ndistinguishable from that found in HbS, HbC and HbS-Oman cells. We conclude that the erythrocytic pathogenesis of HbO(ARAB) involves the de hydration of red cells due, at least in part, to the K:CI cotransport syste m. The similarity of the charge and consequences of the presence of both Hb C and HbO(ARAB), which are the products of mutations at opposite ends of th e beta-chain, raises the possibility that this pathology is the result of a charge-dependent interaction of these haemoglobins with the red cell membr ane and/or its cytoskeleton and that this abnormality is present early in r ed cell development.