Cryptococcus neoformans-reactive and total immunoglobulin profiles of human immunodeficiency virus-infected and uninfected Ugandans

We determined total and Cryptococcus neoformans glucuronoxylomannan (GXM)-reactive antibody repertoires of human immunodeficiency virus (HIV)-infected and HIV-uninfected Ugandans in a retrospective, case-control study of participants in a randomized controlled trial of pneumococcal vaccination. The study included 192 adults: 48 who subsequently developed cryptococcal meningitis (CM); (HIV⁺ CM⁺); 2 individuals who matched them in CD4⁺ T-cell level, stage of HIV disease, and age but did not develop CM (HIV⁺ CM^-); and 48 HIV-uninfected individuals. Total serum immunoglobulin concentrations and titers of immunoglobulin M (IgM), IgG, and IgA to GXM, pneumococcal polysaccharides, and antibodies expressing certain V_H3 idiotypes were determined with banked sera obtained before the development of cryptococcosis for HIV ⁺ CM⁺ subjects. The results showed that HIV-infected subjects had significantly lower levels of IgM to GXM but higher levels of total immunoglobulin and IgG and IgA to GXM than those of HIV-uninfected subjects. HIV-infected subjects with a history of pneumonia had higher levels, and those with a history of herpes zoster had lower levels of GXM-binding antibodies than subjects with no history of either disease. Minimal to no cross-reactivity was demonstrated between antibodies to GXM and polysaccharides in a pneumococcal vaccine. No significant differences between the antibody repertoires of HIV ⁺ CM⁺ and HIV⁺ CM^- subjects were identified, but among subjects without a history of pneumonia, there was a trend towards lower V_H3-positive antibody levels among HIV⁺ CM⁺ than among HIV⁺ CM^- subjects. Our findings demonstrate an association between previous infectious diseases and differences in the total and GXM-reactive antibody repertoires of HIV-infected subjects and suggest the question of whether certain microbes modulate subsequent antibody responses to GXM deserves further study.