Abstract
The predominant immunological finding in HIV+ haemophilia patients is a decrease of CD4+ lymphocytes during progression of the disease. Depletion of CD4+ lymphocytes is paralleled by an increase in the proportion of immune complex-coated CD4+ cells. We examined the hypothesis that the formation of immune complexes on CD4+ lymphocytes is followed by rapid clearance of immune complex-coated CD4+ lymphocytes from the circulation. In this study, the relationship of relative to absolute numbers of immune complex-loaded CD4+ blood lymphocytes and their association with viral load were studied. Two measurements of relative and absolute numbers of gp120-, IgG- and/or IgM-loaded CD4+ lymphocytes were analysed in HIV+ and HIV- haemophilia patients, with a median interval of approx. 3 years. Immune complexes on CD4+ lymphocytes were determined using double-fluorescence flow cytometry and whole blood samples. Viral load was assessed using NASBA and Nuclisens kits. Whereas the proportion of immune complex-coated CD4+ lymphocytes increased with progression of the disease, absolute numbers of immune complex-coated CD4+ lymphocytes in the blood were consistently low. Relative increases of immune complex-coated CD4+ blood lymphocytes were significantly associated with decreases of absolute numbers of circulating CD4+ lymphocytes. The gp120 load on CD4+ blood lymphocytes increased in parallel with the viral load in the blood. These results indicate that immune complex-coated CD4+ lymphocytes are rapidly cleared from the circulation, suggesting that CD4+ reactive autoantibodies and immune complexes are relevant factors in the pathogenesis of AIDS. Relative increases of immune complex-positive cells seem to be a consequence of both an increasing retroviral activity as well as a stronger loading with immune complexes of the reduced number of CD4+ cells remaining during the process of CD4 depletion. The two mechanisms seem to enhance each other and contribute to the progressive CD4 decrease during the course of the disease.