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

Surya Kumari Vadrevu, Irena Trbojevic-Akmacic, Andrew V. Kossenkov, Florent Colomb, Leila B. Giron, Alitzel Anzurez, Kenneth Lynn, Karam Mounzer, Alan L. Landay, Robert C. Kaplan, Emmanouil Papasavvas, Luis J. Montaner, Gordan Lauc, Mohamed Abdel-Mohsen

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish (US)
JournalJournal of Leukocyte Biology
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Immunoglobulin G
HIV
Antibody-Dependent Cell Cytotoxicity
Glycomics
Polysaccharides
T-Lymphocytes
Anti-Inflammatory Agents
Therapeutics
Glycosylation
HIV Infections
Antibodies
RNA
DNA
CD4 Lymphocyte Count
Inflammation

Keywords

  • Fucosylation
  • HIV latency
  • IgG glycosylation
  • Plasma glycosylation
  • Sialylation

ASJC Scopus subject areas

  • Immunology
  • Cell Biology

Cite this

Vadrevu, S. K., Trbojevic-Akmacic, I., Kossenkov, A. V., Colomb, F., Giron, L. B., Anzurez, A., ... Abdel-Mohsen, M. (Accepted/In press). Frontline Science: Plasma and immunoglobulin G galactosylation associate with HIV persistence during antiretroviral therapy. Journal of Leukocyte Biology. https://doi.org/10.1002/JLB.3HI1217-500R

Frontline Science : Plasma and immunoglobulin G galactosylation associate with HIV persistence during antiretroviral therapy. / Vadrevu, Surya Kumari; Trbojevic-Akmacic, Irena; Kossenkov, Andrew V.; Colomb, Florent; Giron, Leila B.; Anzurez, Alitzel; Lynn, Kenneth; Mounzer, Karam; Landay, Alan L.; Kaplan, Robert C.; Papasavvas, Emmanouil; Montaner, Luis J.; Lauc, Gordan; Abdel-Mohsen, Mohamed.

In: Journal of Leukocyte Biology, 01.01.2018.

Research output: Contribution to journalArticle

Vadrevu, SK, Trbojevic-Akmacic, I, Kossenkov, AV, Colomb, F, Giron, LB, Anzurez, A, Lynn, K, Mounzer, K, Landay, AL, Kaplan, RC, Papasavvas, E, Montaner, LJ, Lauc, G & Abdel-Mohsen, M 2018, 'Frontline Science: Plasma and immunoglobulin G galactosylation associate with HIV persistence during antiretroviral therapy', Journal of Leukocyte Biology. https://doi.org/10.1002/JLB.3HI1217-500R
Vadrevu, Surya Kumari ; Trbojevic-Akmacic, Irena ; Kossenkov, Andrew V. ; Colomb, Florent ; Giron, Leila B. ; Anzurez, Alitzel ; Lynn, Kenneth ; Mounzer, Karam ; Landay, Alan L. ; Kaplan, Robert C. ; Papasavvas, Emmanouil ; Montaner, Luis J. ; Lauc, Gordan ; Abdel-Mohsen, Mohamed. / Frontline Science : Plasma and immunoglobulin G galactosylation associate with HIV persistence during antiretroviral therapy. In: Journal of Leukocyte Biology. 2018.
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