ACTIVATION OF MONOCYTES FOR THE IMMUNE CLEARANCE OF RED-CELLS IN BETA-O-THALASSEMIA HBE

We have recently provided evidence that IgG antibodies play a role in the destruction of red cells in thalassaemia syndromes. In order furth er to delineate factors involved in the clearance of thalassaemic cell s, monocytes of 30 Thai patients with beta-degrees-thal/HbE (17 non-sp lenectomized and 13 splenectomized) and 16 normal controls were examin ed for their ability to bind and phagocytose normal red cells coated w ith IgG anti-Rh(D). In beta-degrees-thal/HbE, the mean number of red c ells attached to the monocytes was approximately 3-fold greater than i n normal controls and the number ingested 30% higher. Among the non-sp lenectomized patients, the number of red cells attached to and ingeste d by the monocytes, correlated inversely with mean basal Hb levels, su ggesting that activation of mononuclear phagocytes for the immune clea rance of red cells is a factor in determining the severity of the anae mia. As Fc-gamma-RI is of primary importance in the recognition of IgG -coated red cells by monocytes, leucocytes from 10 beta-degrees-thal/H bE patients (four non-splenectomized and six splenectomized) and five normal controls were investigated for their expression of Fc-gamma-RI by flow cytometry. In beta-degrees-thal/HbE there was an approximately 3-fold increase in the percentage of leucocytes expressing this recep tor: the receptor was up-regulated on monocytes and induced on granulo cytes. The up-regulation of Fc-gamma-RI in beta-degrees-thal/HbE is li kely to be an important component in the activation of monocytes and i n mediating their enhanced effector function towards antibody-coated c ells.