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

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

article

Surya Kumari Vadrevu¹  Irena Trbojevic-Akmacic²  Andrew V. Kossenkov¹  Florent Colomb¹  Leila B. Giron¹  Alitzel Anzurez¹  Kenneth Lynn¹  Karam Mounzer⁴  Alan L. Landay⁵  Robert C. Kaplan⁶  Emmanouil Papasavvas¹  Luis J. Montaner¹  Gordan Lauc²  Mohamed Abdel-Mohsen¹ 

[1] The Wistar Institute;Genos Glycoscience Research Laboratory;Department of Medicine, University of Pennsylvania;Jonathan Lax Center;Department of Microbial Pathogens and Immunity, Rush University Medical Center;Albert Einstein College of Medicine;Faculty of Pharmacy and Biochemistry, University of Zagreb

关键词: fucosylation;    HIV latency;    IgG glycosylation;    plasma glycosylation;    sialylation;   

DOI  :  10.1002/JLB.3HI1217-500R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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 antiinflammatory 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 antiinflammatory 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.

【 授权许可】

CC BY