Comparative Analysis of Glucuronoxylomannogalactan and Glucuronoxylomannan Antibody Responses and Their Associations With Cryptococcal Disease Status in People With HIV

Background. Cryptococcosis remains a major cause of mortality in people with HIV (PWH). While glucuronoxylomannanbinding immunoglobulin G (GXM-IgG) levels have been associated with disease status and survival, the clinical significance of glucuronoxylomannogalactan-binding IgG (GXMGal-IgG) has not been investigated. Methods. We analyzed serological data from 2 previously reported cohorts of PWH: a prospective asymptomatic South African cohort (67 cryptococcal antigen [CrAg] positive, 130 CrAg negative), and a Vietnamese case-control cohort (30 with symptomatic cryptococcal meningitis [CM], 30 without), both followed for mortality for 6 months. Serum/plasma GXMGal-IgG levels were quantified by enzyme-linked immunosorbent assay and compared to previously reported GXM-IgG levels. Logistic regression adjusted for age, sex, and CD4 count examined associations between antibody levels and CrAg positivity or CM status, while Cox proportional hazards models adjusted for CD4 count estimated associations with time to mortality. Results. Higher GXMGal-IgG was associated with CrAg positivity (odds ratio, 1.64; 95% confidence interval [CI], 1.14–2.36), not CM status. Among individuals with asymptomatic cryptococcal antigenemia, higher GXMGal-IgG trended toward higher survival (hazards ratio, 0.67; 95% CI, .41–1.09), but this was not statistically significant and no significant survival benefit was observed for those with CM. Conclusions. GXMGal-IgG was associated with CrAg positivity and showed a modest trend toward survival for individuals with asymptomatic cryptococcal antigenemia but had limited predictive value for CM or mortality. These findings in antigenemia largely parallel previous observations for GXM-IgG, although associations observed were generally weaker. Further studies are needed to clarify the immune response to GXMGal and its potential diagnostic or prognostic significance.