Nature Communications (Apr 2024)
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. 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
Affiliations
- Leila B. Giron
- The Wistar Institute
- Qin Liu
- The Wistar Institute
- Opeyemi S. Adeniji
- The Wistar Institute
- Xiangfan Yin
- The Wistar Institute
- Toshitha Kannan
- The Wistar Institute
- Jianyi Ding
- The Wistar Institute
- David Y. Lu
- The Wistar Institute
- Susan Langan
- Johns Hopkins University
- Jinbing Zhang
- Johns Hopkins University
- Joao L. L. C. Azevedo
- The Wistar Institute
- Shuk Hang Li
- University of Pennsylvania Perelman School of Medicine
- Sergei Shalygin
- University of Georgia
- Parastoo Azadi
- University of Georgia
- David B. Hanna
- Albert Einstein College of Medicine
- Igho Ofotokun
- Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine
- Jason Lazar
- SUNY Downstate Health Sciences University
- Margaret A. Fischl
- Division of Infectious Disease, Department of Medicine, University of Miami
- Sabina Haberlen
- Johns Hopkins University
- Bernard Macatangay
- University of Pittsburgh
- Adaora A. Adimora
- University of North Carolina
- Beth D. Jamieson
- University of California, Los Angeles
- Charles Rinaldo
- University of Pittsburgh
- Daniel Merenstein
- Georgetown University Medical Center
- Nadia R. Roan
- Gladstone Institutes
- Olaf Kutsch
- University of Alabama at Birmingham
- Stephen Gange
- Johns Hopkins University
- Steven M. Wolinsky
- Northwestern University
- Mallory D. Witt
- Lundquist Institute of Biomedical Research at Harbor-UCLA Medical Center
- Wendy S. Post
- Johns Hopkins University
- Andrew Kossenkov
- The Wistar Institute
- Alan L. Landay
- Rush University
- Ian Frank
- University of Pennsylvania Perelman School of Medicine
- Phyllis C. Tien
- University of California San Francisco
- Robert Gross
- University of Pennsylvania Perelman School of Medicine
- Todd T. Brown
- Johns Hopkins University
- Mohamed Abdel-Mohsen
- The Wistar Institute
- DOI
- https://doi.org/10.1038/s41467-024-47279-4
- Journal volume & issue
-
Vol. 15,
no. 1
pp. 1 – 23
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.
