Immunoglobulin G N-glycan markers of accelerated biological aging during chronic HIV infection
-
Published:2024-04-10
Issue:1
Volume:15
Page:
-
ISSN:2041-1723
-
Container-title:Nature Communications
-
language:en
-
Short-container-title:Nat Commun
Author:
Giron Leila B.ORCID, Liu QinORCID, Adeniji Opeyemi S., Yin Xiangfan, Kannan ToshithaORCID, Ding Jianyi, Lu David Y., Langan Susan, Zhang Jinbing, Azevedo Joao L. L. C., Li Shuk HangORCID, Shalygin SergeiORCID, Azadi Parastoo, Hanna David B., Ofotokun Igho, Lazar Jason, Fischl Margaret A., Haberlen Sabina, Macatangay Bernard, Adimora Adaora A., Jamieson Beth D.ORCID, Rinaldo Charles, Merenstein Daniel, Roan Nadia R.ORCID, Kutsch Olaf, Gange StephenORCID, Wolinsky Steven M., Witt Mallory D., Post Wendy S., Kossenkov Andrew, Landay Alan L., Frank Ian, Tien Phyllis C., Gross Robert, Brown Todd T., Abdel-Mohsen MohamedORCID
Abstract
AbstractPeople 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.
Publisher
Springer Science and Business Media LLC
Reference112 articles.
1. Roomaney, R. A., van Wyk, B. & Pillay-van Wyk, V. Aging with HIV: increased risk of HIV comorbidities in older adults. Int. J. Environ. Res. Public Health 19, 2359 (2022). 2. Franceschi, C. & Campisi, J. Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J. Gerontol. A Biolmed. Sci. Med. Sci. 69, S4–S9 (2014). 3. Nasi, M. et al. Ageing and inflammation in patients with HIV infection. Clin. Exp. Immunol. 187, 44–52 (2017). 4. Minciullo, P. L. et al. Inflammaging and anti-inflammaging: the role of cytokines in extreme longevity. Arch. Immunol. Ther. Exp. 64, 111–126 (2016). 5. Nixon, D. E. & Landay, A. L. Biomarkers of immune dysfunction in HIV. Curr. Opin. HIV AIDS 5, 498–503 (2010).
|
|