AbstractWe reported recently that anti‐Fab autoantibodies of the IgG isotype are associated with the decrease of helper/inducer (CD4+) lymphocytes in human immunodeficiency virus‐infected (HIV+) hemophilia patients with acquired immunodeficiency syndrome (AIDS) or AIDS‐related complex (ARC). In the present study we investigated the subclass distribution of IgG‐anti‐Fab autoantibodies, and whether anti‐Fab antibodies of the IgA 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 HIV+ patients with ARC (p<0.02), HIV+ patients without AIDS/ARC (p<0.0001), HIV‐negative (HIV‐) patients (p<0.001), or healthy controls (p<0.0001). An inverse association was found between IgA‐anti‐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. However, IgM‐anti‐Fab was significantly increased in patients with thrombocytopenia. We found a significant association between IgA‐anti‐Fab activity and serum neopterin concentrations (r = 0.310, p<10‐5). IgG‐anti‐Fab activity was detected mainly in the IgG3 fraction, although in HIV+ patients with AIDS/ARC various IgG subclasses were present. Affinity‐purified anti‐Fab antibodies isolated from sera of AIDS patients bound to rgp120‐preincubated CD4+ cells of a healthy individual, supporting our hypothesis that anti‐Fab antibodies and free circulating gp120 molecules are involved in the elimination of uninfected CD4+ cells. Removal of anti‐Fab autoantibodies from the circulation by immune adsorba