학술논문
Immunoglobulin G N-glycan markers of accelerated biological aging during chronic HIV infection
Document Type
article
Author
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
Source
Nature Communications, Vol 15, Iss 1, Pp 1-23 (2024)
Subject
Language
English
ISSN
2041-1723
Abstract
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.