Humoral Aspects of Anti-HIV Immune Responses in Zairians with AIDS: Lower Antigenemia Does Not Correlate with Immune Complex Levels

Abstract

Serological patterns of anti-HIV immune responses of 150 HIV-infected (65 asymptomatic, 19 ARC, 66 AIDS) and 150 HIV-negative healthy Zairians were studied to determine the clinical significance of p24 antigen, and anti-p24 antibody, particularly in relation to p24 relative binding capacity (RBC) and circulating immune complexes (CICs). Levels of p24 antigen, anti-p24 antibody titers, and p24 RBC were evaluated by means of enzyme-linked immunosorbent assay (ELISA). Circulating immune complexes were measured by C1q-binding assay. Human immunodeficiency virus CICs were detected by polyethylene glycol (PEG) precipitation followed by 6 M guanidinium lysis, ELISA, Western blot, or radioimmunoprecipitation of the lysed precipitates. Immunoglobulin levels for IgG, IgM, IgA, and β₂-microglobulin (β₂-M) were quantified in all study participants by laser nephelometry and ELISA. All immunoglobulin levels were significantly elevated among HIV-positive vs. HIV-negative individuals. Immunoglobulin levels correlated well with disease progression among infected patients. Similarly, β₂-M levels were significantly higher in HIV-positive vs. HIV-negative individuals and correlated well with progression to AIDS. Free p24 antigen in serum was detected in 1.33% of all patients. However, p24 reactivity increased to 6% (9 of 150 cases) after PEG precipitation and CIC dissociation. There was a good correlation between p24 reactivity and disease development. High titers of anti-p24 antibody (>44,100) occurred in at least 80% of all patients, and did not correlate with disease stage. Similarly, more than 60% of patients had high levels of p24 RBC. Although CICs were frequently detected in HIV-positive patients, the frequency of HIV-specific CICs was low. Western blot and radioimmunoassay analysis of PEG precipitates showed the presence of antibodies to all Gag, Pol, and Env proteins, suggesting that all HIV products can be trapped in CICs. These results confirm the low prevalence of p24 antigen in Africans, and suggest that low antigenemia may not be attributable solely to CIC formation.