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

Abstract

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.

Abstract

Diverging bulk IgG N‐linked glycan profiles are observed 8 weeks following Mycobacterium tuberculosis (Mtb) infection in simian immunodeficiency virus (SIV)‐naïve and SIV‐coinfected macaques.