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J Leukoc Biol. 2018 Sep;104(3):461-471. doi: 10.1002/JLB.3HI1217-500R. Epub 2018 Apr 6.

Frontline Science: Plasma and immunoglobulin G galactosylation associate with HIV persistence during antiretroviral therapy.

Author information

1
The Wistar Institute, Philadelphia, Pennsylvania, USA.
2
Genos Glycoscience Research Laboratory, Zagreb, Croatia.
3
Department of Medicine, University of Pennsylvania, Pennsylvania, USA.
4
Jonathan Lax Center, Philadelphia FIGHT, Pennsylvania, USA.
5
Department of Microbial Pathogens and Immunity, Rush University Medical Center, Chicago, Illinois, USA.
6
Albert Einstein College of Medicine, Bronx, New York, USA.
7
Faculty of Pharmacy and Biochemistry, University of Zagreb, Zagreb, Croatia.

Abstract

Global antibody glycosylation is dynamic and plays critical roles in shaping different immunological outcomes and direct antibody functionality during HIV infection. However, the relevance of global antibody or plasma glycosylation patterns to HIV persistence after antiretroviral therapy (ART) has not been characterized. First, we compared glycomes of total plasma and isolated immunoglobulin G (IgG) from HIV+ ART-suppressed, HIV+ viremic, and HIV-negative individuals. Second, in ART-suppressed individuals, we examined the associations between glycomes and (1) levels of cell-associated HIV DNA and RNA in PBMCs and isolated CD4+ T cells, (2) CD4 count and CD4%, and (3) expression of CD4+ T-cell activation markers. HIV infection is associated with persistent alterations in the IgG glycome including decreased levels of disialylated glycans, which is associated with a lower anti-inflammatory activity, and increased levels of fucosylated glycans, which is associated with lower antibody-dependent cell-mediated cytotoxicity (ADCC). We also show that levels of certain mono- and digalactosylated nonfucosylated glycomic traits (A2G1, A2G2, and A2BG2), which have been reported to be associated with higher ADCC and higher anti-inflammatory activities, exhibit significant negative correlations with levels of cell-associated total HIV DNA and HIV RNA in ART-suppressed individuals. Finally, levels of certain circulating anti-inflammatory glycans are associated with higher levels of CD4 T cells and lower levels of T-cell activation. Our findings represent the first proof-of-concept evidence that glycomic alterations, known to be associated with differential states of inflammation and ADCC activities, are also associated with levels of HIV persistence in the setting of ART suppression.

KEYWORDS:

HIV latency; IgG glycosylation; fucosylation; plasma glycosylation; sialylation

PMID:
29633346
PMCID:
PMC6113120
DOI:
10.1002/JLB.3HI1217-500R
[Indexed for MEDLINE]
Free PMC Article

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