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 separat ely 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 acti vity was predominantly observed with IgA from asymptomatic HIV-seropos itive 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 wi th a mAb specific for the Fc alpha receptor. Concentrations of IgG med iating ADE were generally present in sera at dilutions from 10(-4) to 10(-6). When Ige was adjusted to physiologic concentration and combine d with an enhancing concentration of IgA, enhancement was not observed unless IgG was also present at a concentration which exhibited this a ctivity. These results suggest that, in comparison with Igc, HIV-infec ted individuals more often produce IgA Abs reacting with enhancing det erminants of HIV. IgA-mediated ADE of HIV infection may not play a sig nificant 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 cel ls 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.