Plasma Glycomic Markers of Accelerated Biological Aging During Chronic HIV Infection.

Autor:	Giron LB; The Wistar Institute, Philadelphia, PA, USA., Liu Q; The Wistar Institute, Philadelphia, PA, USA., Adeniji OS; The Wistar Institute, Philadelphia, PA, USA., Yin X; The Wistar Institute, Philadelphia, PA, USA., Kannan T; The Wistar Institute, Philadelphia, PA, USA., Ding J; The Wistar Institute, Philadelphia, PA, USA., Lu DY; The Wistar Institute, Philadelphia, PA, USA.; Cornell University, New York, NY, USA., Langan S; Johns Hopkins University, Baltimore, MD, USA., Zhang J; Johns Hopkins University, Baltimore, MD, USA., Azevedo JLLC; The Wistar Institute, Philadelphia, PA, USA., Li SH; University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA., Shalygin S; University of Georgia, Athens, Georgia, USA., Azadi P; University of Georgia, Athens, Georgia, USA., Hanna DB; Albert Einstein College of Medicine, Bronx, NY, USA., Ofotokun I; Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA., Lazar J; SUNY Downstate Health Sciences University, New York, NY, USA., Fischl MA; University of Miami, Miami, FL, USA., Haberlen S; Johns Hopkins University, Baltimore, MD, USA., Macatangay B; University of Pittsburgh, Pittsburgh, PA, USA., Adimora AA; University of North Carolina, Chapel Hill, NC, USA., Jamieson BD; University of California, Los Angeles, Los Angeles, CA, USA., Rinaldo C; University of Pittsburgh, Pittsburgh, PA, USA., Merenstein D; Georgetown University Medical Center, Washington, DC, USA., Roan NR; Gladstone Institutes, San Francisco, CA, USA.; University of California San Francisco, San Francisco, CA, USA., Kutsch O; University of Alabama at Birmingham, Birmingham, Alabama, USA., Gange S; Johns Hopkins University, Baltimore, MD, USA., Wolinsky S; Northwestern University, Evanston, IL, USA., Witt M; Los Angeles Biomedical Research Institute, Torrance, CA, USA., Post WS; Johns Hopkins University, Baltimore, MD, USA., Kossenkov A; The Wistar Institute, Philadelphia, PA, USA., Landay A; Rush University, Chicago, IL, USA., Frank I; University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA., Tien PC; University of California San Francisco, San Francisco, CA, USA., Gross R; University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA., Brown TT; Johns Hopkins University, Baltimore, MD, USA., Abdel-Mohsen M; The Wistar Institute, Philadelphia, PA, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2023 Dec 31. Date of Electronic Publication: 2023 Dec 31.
DOI:	10.1101/2023.08.09.551369
Abstrakt:	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. Competing Interests: COMPETING INTERESTS STATEMENT The authors have no competing interests.
Databáze:	MEDLINE
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