title: CD4 depletion in HIV-infected haemophilia patients is associated with rapid clearance of immune complex-coated CD4+ lymphocytes.
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.
authors: Department of Transplantation Immunology, University of Heidelberg, Germany. Volker_Daniel@UKL.uni-heidelberg.de
authors: V
authors: V
authors: Daniel
authors: A
authors: A
authors: Melk
authors: C
authors: C
authors: Süsal
authors: R
authors: R
authors: Weimer
authors: R
authors: R
authors: Zimmermann
authors: A
authors: A
authors: Huth-Kühne
authors: G
authors: G
authors: Opelz
mesh_terms: D000936:Antigen-Antibody Complex / Q000097:blood*; D015704:CD4 Antigens / Q000097:blood*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D015658:HIV Infections / Q000150:complications* / Q000276:immunology*; D018023:HIV Seronegativity / Q000276:immunology; D006467:Hemophilia A / Q000150:complications* / Q000276:immunology*; D006801:Humans; D008231:Lymphopenia / Q000276:immunology; D008297:Male; D013997:Time Factors; D014766:Viremia / Q000276:immunology
chemical_list: D000936:Antigen-Antibody Complex; D015704:CD4 Antigens