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Case Reports
, 115 (3), 477-84

CD4 Depletion in HIV-infected Haemophilia Patients Is Associated With Rapid Clearance of Immune Complex-Coated CD4+ Lymphocytes

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Case Reports

CD4 Depletion in HIV-infected Haemophilia Patients Is Associated With Rapid Clearance of Immune Complex-Coated CD4+ Lymphocytes

V Daniel et al. Clin Exp Immunol.

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.

Figures

Fig. 1
Fig. 1
Patient with low gp120 load on CD4+ blood lymphocytes. CD4+ lymphocytes of patient A decreased from 990/μl in 1992 to 207/μl in 1996. Increases of CD4+gp120+ lymphocytes were associated with decreases of the CD4+ cell counts. The CD4+ cell decrease in 1995/96 was associated with the second highest relative and absolute rise of CD4+gp120+ cells during the observation period. The CD4+gp120+ cells peaked at 27%, the absolute counts of CD4+gp120+ lymphocytes at 91/μl.
Fig. 2
Fig. 2
Patient with high gp120 load on CD4+ blood lymphocytes. CD4+ lymphocytes of patient B decreased from 586/μl to 8/μl during the course of the disease. When CD4+ lymphocytes dropped < 300/μl in 1994, CD4+gp120+ cells became detectable, with peak increases to 99% during periods of extremely low CD4+ lymphocyte counts. The CD4+gp120+ lymphocyte counts were < 50/μl with two exceptions in 1991 and 1994.
Fig. 3
Fig. 3
Patient with high gp120 load on CD4+ blood lymphocytes followed by a decrease of the gp120 load and an increase of CD4+ blood lymphocyte counts. Patient C had 231 CD4+ lymphocytes/μl in 1992. The CD4+ lymphocyte count decreased to five CD4+ cells/μl in 1995/96 and increased to 113 CD4+ cells/μl in 1996/97 after the initiation of triple-drug treatment. During periods of extremely low CD4+ cell numbers the patient had 30–80% CD4+gp120+ cells. When CD4+gp120+ cells decreased in 1996/97, CD4+ cells increased again and began to fluctuate during the subsequent period of increasing CD4+gp120+ lymphocytes. CD4+gp120+ lymphocytes were stable at levels of < 50/μl with one exception in 1990.
Fig. 4
Fig. 4
Patient with strongly fluctuating CD4+ lymphocyte counts and inverse association of CD4+gp120+ lymphocytes. Patient D showed strongly fluctuating CD4+ lymphocyte counts during 1989–98 with inverse associations of CD4+gp120+ lymphocytes. Although relative numbers of CD4+gp120+ lymphocytes increased to 48%, CD4+ gp120+ cell counts were consistently < 100/μl.

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