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

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

Nature communications (2024-04-11)
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 Adimora, Beth 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
PMID38600088
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.