ISOTYPES AND IGG SUBCLASSES OF ANTI-FAB ANTIBODIES IN HUMAN IMMUNODEFICIENCY VIRUS-INFECTED HEMOPHILIA PATIENTS

We reported recently that anti-Fab autoantibodies of the IgG isotype a re associated with the decrease of helper/inducer (CD4+) lymphocytes i n human immunodeficiency virus-infected (HIV+) hemophilia patients wit h acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (A RC). In the present study we investigated the subclass distribution of IgG-anti-Fab autoantibodies, and whether anti-Fab antibodies of the I gA and IgM isotypes also are associated with the development of AIDS. Sera of HIV+ patients with AIDS had significantly higher IgA-anti-Fab activity than HIVS patients with ARC (p<0.02), HIV+ patients without A IDS/ARC (p<0.0001), HIV-negative (HIV-) patients (p<0.001), or healthy controls (p<0.0001). An inverse association was found between IgA-ant i-Fab activity and CD4+ cell counts (r=-0.396, p<10(-6)). In contrast, no association of CD4+ cell counts was observed with IgM-anti-Fab. Ho wever, IgM-anti-Fab was significantly increased in patients with throm bocytopenia. We found a significant association between IgA-anti-Fab a ctivity and serum neopterin concentrations (r=0.310, p<10(-5)). IgG-an ti-Fab activity was detected mainly in the IgG3 fraction, although in HIVS patients with AIDS/ARC various IgG subclasses were present. Affin ity-purified anti-Fab antibodies isolated from sera of AIDS patients b ound to rgp120-preincubated CD4+ cells of a healthy individual, suppor ting our hypothesis that anti-Fab antibodies and free circulating gp12 0 molecules are involved in the elimination of uninfected CD4+ cells. Removal of anti-Fab autoantibodies from the circulation by immune adso rbance might be a useful approach in the treatment of AIDS.