Immunoglobulin G N-glycan markers of accelerated biological aging during chronic HIV infection

Leila B. Giron, Qin Liu, Opeyemi S. Adeniji, Xiangfan Yin, Toshitha Kannan, Jianyi Ding, David Y. Lu, Susan Langan, Jinbing Zhang, Joao L.L.C. Azevedo, Shuk Hang Li, Sergei Shalygin, Parastoo Azadi, David B. Hanna, Igho Ofotokun, Jason Lazar, Margaret A. Fischl, Sabina Haberlen, Bernard Macatangay, Adaora A. AdimoraBeth D. Jamieson, Charles Rinaldo, Daniel Merenstein, Nadia R. Roan, Olaf Kutsch, Stephen Gange, Steven M. Wolinsky, Mallory D. Witt, Wendy S. Post, Andrew Kossenkov, Alan L. Landay, Ian Frank, Phyllis C. Tien, Robert Gross, Todd T. Brown, Mohamed Abdel-Mohsen

Research output: Contribution to journalArticlepeer-review

Abstract

People living with HIV (PLWH) experience increased vulnerability to premature aging and inflammation-associated comorbidities, even when HIV replication is suppressed by antiretroviral therapy (ART). However, the factors associated with this vulnerability remain uncertain. In the general population, alterations in the N-glycans on IgGs trigger inflammation and precede the onset of aging-associated diseases. Here, we investigate the IgG N-glycans in cross-sectional and longitudinal samples from 1214 women and men, living with and without HIV. PLWH exhibit an accelerated accumulation of pro-aging-associated glycan alterations and heightened expression of senescence-associated glycan-degrading enzymes compared to controls. These alterations correlate with elevated markers of inflammation and the severity of comorbidities, potentially preceding the development of such comorbidities. Mechanistically, HIV-specific antibodies glycoengineered with these alterations exhibit a reduced ability to elicit anti-HIV Fc-mediated immune activities. These findings hold potential for the development of biomarkers and tools to identify and prevent premature aging and comorbidities in PLWH.

Original languageEnglish (US)
Article number3035
JournalNature communications
Volume15
Issue number1
DOIs
StatePublished - Dec 2024
Externally publishedYes

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy

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