Hepatitis C virus modulates IgG glycosylation in HIV co-infected antiretroviral therapy suppressed individuals.

OBJECTIVE

Glycosylation plays a critical role in mediating several antibody (mainly immunoglobulin G; IgG) immunological functions, including antibody-dependent cell-mediated cytotoxicity (ADCC), and anti-inflammatory activities. We investigated whether IgG glycosylation and immune profile patterns are differentially modulated in mono and dual infection using samples from untreated hepatitis C virus (HCV)-infected individuals with and without co-infection with antiretroviral therapy (ART)-suppressed HIV.

DESIGN

IgG glycosylation, immune subsets, natural killer cell function, and liver enzymes were assessed in 14 HCV mono-infected and 27 ART-suppressed HIV/HCV co-infected participants naïve to HCV treatment. Historic IgG glycosylation data from 23 ART-suppressed chronically HIV-infected individuals were also used for comparisons.

METHODS

Plasma IgG glycosylation was assessed using capillary electrophoresis. Whole blood was used for immune subset characterization by flow cytometry. Peripheral blood mononuclear cells were used to measure constitutive and interferon-α-induced K562 target cell lysis. Statistical analysis was performed using R (3.5.0).

RESULTS

HIV/HCV had lower levels of pro-ADCC-associated nonfucosylated glycans when compared with HIV [e.g. di-sialylated A2 percentage (%): P = 0.04], and higher levels of T and myeloid cell activation/exhaustion when compared with HCV (e.g. CD3CD8CD38 %: P < 0.001). Finally, in HCV high levels of the anti-inflammatory galactosylated and sialylated glycans were associated with low plasma levels of aspartate aminotransferase (AST), low CD8 T-cell activation, and high CD8 T-cell exhaustion.

CONCLUSION

HCV modulates IgG glycosylation profile in HIV co-infected individuals on suppressive ART. These results could inform on the modulation of IgG glycans in other mono and dual infections.