CD4 depletion in HIV‐infected haemophilia patients is associated with rapid clearance of immune complex‐coated CD4+ lymphocytes

• Published in: Clinical and experimental immunology Vol. 115; no. 3; pp. 477 - 484
• Main Authors: DANIEL, V, MELK, A, SÜSAL, C, WEIMER, R, ZIMMERMANN, R, HUTH-KÜHNE, A, OPELZ, G
• Format: Journal Article
• Language: English
• Published: Oxford BSL Blackwell Science Ltd 01.03.1999; Blackwell; Oxford University Press; Blackwell Science Inc
• Subjects: AIDS/HIV; Antigen-Antibody Complex - blood; autoimmunity; Biological and medical sciences; Case-Control Studies; CD4 Antigens - blood; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes - immunology; Hemophilia A - complications; Hemophilia A - immunology; HIV; HIV Infections - complications; HIV Infections - immunology; HIV Seronegativity - immunology; Human viral diseases; Humans; immune complex load; Infectious diseases; Lymphopenia - immunology; Male; Medical sciences; Original; Time Factors; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; viral load; Viremia - immunology; Human; Immunopathology; Immune response; Pathophysiology; Retroviridae; Helper cell; AIDS; Cellular immunity; Immune deficiency; Lentivirus; Cell subpopulation; Infection; Virus; Immunological investigation; Viral disease; T-Lymphocyte; Human immunodeficiency virus; Viral load; Immune complex
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1046/j.1365-2249.1999.00848.x

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.