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

作者：Surya Kumari Vadrevu, Irena Trbojević‐Akmačić, Andrew V. Kossenkov, Florent Colomb, Leila B. Giron, Alitzel Anzurez, Kenneth Lynn, Karam Mounzer, Alan Landay, Robert C. Kaplan, Emmanouil Papasavvas, Luis J. Montaner, Gordan Lauc, Mohamed Abdel‐Mohsen · 发表于：Journal of Leukocyte Biology · 年份：2018 · DOI：10.1002/jlb.3hi1217-500r · 被引用次数：48 · 研究领域：HIV Research and Treatment、Glycosylation and Glycoproteins Research、Immune Cell Function and Interaction

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 cel...