Plasma Glycomic Markers of Accelerated Biological Aging During Chronic HIV Infection

• Authors: Wendy S. Post, Johns Hopkins University; Andrew Kossenkov, The Wistar Institute; Alan Landay, Rush University; Ian Frank, University of Pennsylvania; Phyllis C. Tien, University of California San Francisco; Robert Gross, University of Pennsylvania; Todd T. Brown, Johns Hopkins University; Mohamed Abdel-Mohsen, The Wistar Institute; 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; Sergei Shalygin, University of Georgia; Parastoo Azadi, University of Georgia; David B. Hanna, Albert Einstein College of Medicine; Igho Ofotokun, Emory University; Jason Lazar, SUNY Downstate Health Sciences University; Margaret A. Fischl, 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; Nadia R. Roan, University of California San Francisco; Olaf Kutsch, University of Alabama; Stephen Gange, Johns Hopkins University; Steven Wolinsky, Northwestern University; Mallory Witt, Los Angeles Biomedical Research Institute
• Journal Title: bioRxiv
• Publisher: NIH | 2023-08-10
• Type of Work: Article | Preprint: Prior to Peer Review
• Publisher DOI: http://doi.org/10.1101/2023.08.09.551369
• Subjects: Biology, Virology; Health Sciences, Oncology
• Keywords: HIV; Glycome; IgG; Inflammation; Aging; Biological age; Cancer; Subclinical atherosclerosis; ADCC; ADCP; ADCD

Abstract

People with HIV (PWH) experience an increased vulnerability to premature aging and inflammation-associated comorbidities, even when HIV replication is suppressed by antiretroviral therapy (ART). However, the factors that contribute to or are associated with this vulnerability remain uncertain. In the general population, alterations in the glycomes of circulating IgGs trigger inflammation and precede the onset of aging-associated diseases. Here, we investigate the IgG glycomes of cross-sectional and longitudinal samples from 1,216 women and men, both living with virally suppressed HIV and those without HIV. Our glycan-based machine learning models indicate that living with chronic HIV significantly accelerates the accumulation of pro-aging-associated glycomic alterations. Consistently, PWH exhibit heightened expression of senescence-associated glycan-degrading enzymes compared to their controls. These glycomic alterations correlate with elevated markers of inflammatory aging and the severity of comorbidities, potentially preceding the development of such comorbidities. Mechanistically, HIV-specific antibodies glycoengineered with these alterations exhibit reduced anti-HIV IgG-mediated innate immune functions. These findings hold significant potential for the development of glycomic-based biomarkers and tools to identify and prevent premature aging and comorbidities in people living with chronic viral infections.