Antibody glycosylation correlates with disease progression in SIV-Mycobacterium tuberculosis coinfected cynomolgus macaques

Objectives. Tuberculosis (TB) remains a substantial cause of morbidity and mortality among people living with human immunodeficiency virus (HIV) worldwide. However, the immunological mechanisms associated with the enhanced susceptibility among HIV-positive individuals remain largely unknown. Methods. Here, we used a simian immunodeficiency virus (SIV)/TB-coinfection Mauritian cynomolgus macaque (MCM) model to examine humoral responses from the plasma of SIV-negative (n = 8) and SIV-positive (n = 7) MCM 8-week postinfection with Mycobacterium tuberculosis (Mtb).Results. Antibody responses to Mtb were impaired during SIV coinfection. Elevated inflammatory bulk IgG antibody glycosylation patterns were observed in coinfected macaques early at 8-week post-Mtb infection, including increased agalactosylation (G0) and reduced di-galactosylation (G2), which correlated with endpoint Mtb bacterial burden and gross pathology scores, as well as the time-to-necropsy. Conclusion. These studies suggest that humoral immunity may contribute to control of TB disease and support growing literature that highlights antibody Fc glycosylation as a biomarker of TB disease progression.

Automated summary

This study used a macaque model of tuberculosis and HIV co-infection to investigate the humoral responses. They found that antibody responses to tuberculosis were impaired during HIV co-infection. The study suggests that humoral immunity and antibody glycosylation may play a role in the control and progression of tuberculosis.