Anti-IgG Autoantibodies in HIV-Infected Hemophilia Patients

Abstract

Sera of 76 HIV-negative hemophilia patients, 103 HIV-positive (HIV+) hemophilia patients free of AIDS or AIDS related complex (ARC), and 32 HIV+ hemophilia patients with AIDS/ARC were tested for four different anti-IgG activities. IgG-anti-F(ab')(2γ), IgM-anti-F(ab')(2γ), and IgG-anti-Fcγ serum activities were significantly associated with the clinical stage of HIV infection, whereas IgM-anti-Fcγ was not. IgG-anti-F(ab')(2γ) activity was found to be caused by cross-reaction of anti-HIV antibody with an epitope within the constant CH1 domain of human IgG. HIV+ hemophilia patients with severe thrombocytopenia (<50,000/µI platelet counts) had significantly higher IgM- anti-IgG activity than patients with >50,000/µI platelets. Because anti-IgG antibodies possess immunoregulatory properties, our results may serve as a possible explanation for the frequent B cell disorders encountered in HIV- infected patients.

CD4+ Lymphocyte Depletion in HIV-Infected Patients is Associated with gp120-lmmunoglobulin- Complement Attachment to CD4+ Cells

“…There is evidence that viremia is induced during coinfection with other infectious agents by in creased tumor necrosis factor release of monocytes/mac rophages [24][25][26][27][28], activation of HIV-1 LTR [29,30], or by the appearance of HIV mutants with high replication rates [8] and strong CD4 receptor affinity [31][32][33][34][35], Binding of HIV to CD4 induces the release of envelope glycoprotein gpl20 [36,37], Free gpl20 is readily detectable in the pe ripheral blood [38,39]. Circulating gpl20 can react with anti-gpl20 antibodies or with anti-IgG antibodies that cross-react with gpl20 [40,41]. Our data indicate that these gpl20-anti-gpl20 complexes bind to the surface of CD4+ lymphocytes.…”

Isotypes and IgG Subclasses of Anti-Fab Antibodies in Human Immunodeficiency Virus-Infected Hemophilia Patients

“…We have shown that anti-IgG autoantibodies increase with the clinical progression of HIV infection [5], and that the occurrence of anti-Fab autoantibodies of the IgG iso type is associated with decreasing CD4+ lymphocyte counts [6]. In the present study, we investigated the sub class distribution of IgG-anti-Fab autoantibodies and whether anti-Fab antibodies of the IgA and IgM isotypes are also associated with the development of AIDS.…”

Molecular Mimicry between HIV-1 and Antigen Receptor Molecules: A Clue to the Pathogenesis of AIDS

“…However, our finding that anti-Fab antibodies are associated with disease progres sion and loss of CD4+ T cells in HIV-infected patients [13,14] rather argues for the possibility that an immune re sponse against the mimicking epitopes might attack the immune network, which is based on idiotype-antiidiotype stabilization. Alternatively, viral proteins themselves might interact with idiotypes that are complementary to the viral protein sequences and this might lead to a block age of important regulatory cell clones.…”

“…The reactivity against gpl20 is not surprising since there are sequence homologies be tween gpl20 and variable and constant regions of IgG-Fab [16][17][18]. We were able to show that the anti-F(ab')2 activity in sera of HIV-infected patients is at least partly due to cross-reaction of anti-gpl20 antibodies with a homologous sequence in the constant CHI region of the IgG molecule [13]. However, antiidiotypic activity against the variable regions of Ig molecules must also be assumed since homol ogy exists between gpl20 and the variable VH-III region of IgG [16], molecules.…”

“…Herein, we speculate that molecular mimicry between HIV-1 and antigen receptor molecules, We have previously described, first in an experimental rat model and later in humans, that immunization with alloantigens leads to the induction of immunoregulatory autoantibodies directed against the F(ab')2 region of the IgG molecule [9][10][11]. Serum IgG-anti-F(ab')2 activity is associated with good kidney graft outcome, suggesting an immunosuppressive character of these antibodies [10,12], Recently, we described that anti-F(ab')2 autoantibodies in HIV-infected patients are associated with disease progres sion [13]. We found a striking inverse association of IgGanti-Fab autoantibodies and CD4+ T cell counts which became impressively evident in a longitudinal analysis of 16 HIV+ patients who developed AIDS/ARC.…”