High prevalence of serum IgA HIV-1 infection-enhancing antibodies in HIV-infected persons. Masking by IgG.

IgA and IgG purified from sera of 20 HIV-infected persons were separately examined for ability to mediate Ab-dependent enhancement (ADE) of HIV-1 infection of U937 cells. Both isotypes were capable of enhancing infection of these cells. However, IgA from twice as many persons (14/20) displayed infection enhancement when compared with IgG. This activity was predominantly observed with IgA from asymptomatic HIV-seropositive subjects (9/9). Enhanced HIV infection by IgA was observed most often at concentrations equivalent to serum dilutions in the range 10(-3) to 10(-5) and could be inhibited by preincubation of U937 cells with a mAb specific for the Fc alpha receptor. Concentrations of IgG mediating ADE were generally present in sera at dilutions from 10(-4) to 10(-6). When IgG was adjusted to physiologic concentration and combined with an enhancing concentration of IgA, enhancement was not observed unless IgG was also present at a concentration which exhibited this activity. These results suggest that, in comparison with IgG, HIV-infected individuals more often produce IgA Abs reacting with enhancing determinants of HIV. IgA-mediated ADE of HIV infection may not play a significant role in facilitating systemic dissemination of HIV because of the presence of higher concentrations of IgG. However, the production of IgA HIV-enhancing Abs at mucosal sites, where fewer IgG plasma cells are present, could contribute to the pathogenesis of HIV infection and interfere with development of vaccines designed to induce HIV IgA Abs at mucosal surfaces.