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

doi:10.1038/s41467-024-47279-4

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. AdimoraBeth 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^*

^*Corresponding author for this work

Medicine, Infectious Diseases Division

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

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.

Original language	English (US)
Article number	3035
Journal	Nature communications
Volume	15
Issue number	1
DOIs	https://doi.org/10.1038/s41467-024-47279-4
State	Published - Dec 2024

Funding

This work is mainly supported by the NIH R01AG062383 and the NCI supplement to the Wistar Institute Cancer Center (P30 CA010815) to M.A-M. M.A-M. is also funded by the NIH grants, R01AI165079, R01NS117458, R01DK123733, R21AI170166,\u00A0Penn Center for AIDS Research (P30 AI 045008), and the NIH-funded BEAT-HIV Martin Delaney Collaboratory to cure HIV-1 infection (1UM1Al126620)\u00A0as well as the Gates foundation grant #\u00A0Inv-033977. Mass spectrometry based glycomic analyses was partially supported by NIH R24GM137782 and GlycoMIP, a National Science Foundation Materials Innovation Platform funded through Cooperative Agreement DMR-1933525. We Would like to thank Drs. Michel Nussenzweig, Costin Tomescu, and Luis J. Montaner for providing the wild-type 10-1074 for the glycoengineering experiments and Dr. Daniel Kulp for providing HIV-1 Env trimer, BG505. Data in this manuscript were collected by the MACS/WIHS Combined Cohort Study (MWCCS). The contents of this publication are solely the responsibility of the authors and do not represent the official views of the National Institutes of Health (NIH). MWCCS (Principal Investigators): Atlanta CRS (Ighovwerha Ofotokun, Anandi Sheth, and Gina Wingood), U01-HL146241; Baltimore CRS (Todd Brown and Joseph Margolick), U01-HL146201; Bronx CRS (Kathryn Anastos, David Hanna, and Anjali Sharma), U01-HL146204; Brooklyn CRS (Deborah Gustafson and Tracey Wilson), U01-HL146202; Data Analysis and Coordination Center (Gypsyamber D\u2019Souza, Stephen Gange and Elizabeth Topper), U01-HL146193; Chicago-Cook County CRS (Mardge Cohen and Audrey French), U01-HL146245; Chicago-Northwestern CRS (Steven Wolinsky, Frank Palella, and Valentina Stosor), U01-HL146240; Northern California CRS (Bradley Aouizerat, Jennifer Price, and Phyllis Tien), U01-HL146242; Los Angeles CRS (Roger Detels and Matthew Mimiaga), U01-HL146333; Metropolitan Washington CRS (Seble Kassaye and Daniel Merenstein), U01-HL146205; Miami CRS (Maria Alcaide, Margaret Fischl, and Deborah Jones), U01-HL146203; Pittsburgh CRS (Jeremy Martinson and Charles Rinaldo), U01-HL146208; UAB-MS CRS (Mirjam-Colette Kempf, Jodie Dionne-Odom, Deborah Konkle-Parker, and James B. Brock), U01-HL146192; UNC CRS (Adaora Adimora and Michelle Floris-Moore), U01-HL146194. The MWCCS is funded primarily by the National Heart, Lung, and Blood Institute (NHLBI), with additional co-funding from the Eunice Kennedy Shriver National Institute Of Child Health & Human Development (NICHD), National Institute On Aging (NIA), National Institute Of Dental & Craniofacial Research (NIDCR), National Institute Of Allergy And Infectious Diseases (NIAID), National Institute Of Neurological Disorders And Stroke (NINDS), National Institute Of Mental Health (NIMH), National Institute On Drug Abuse (NIDA), National Institute Of Nursing Research (NINR), National Cancer Institute (NCI), National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Institute on Deafness and Other Communication Disorders (NIDCD), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute on Minority Health and Health Disparities (NIMHD), and in coordination and alignment with the research priorities of the National Institutes of Health, Office of AIDS Research (OAR). MWCCS data collection is also supported by UL1-TR000004 (UCSF CTSA), UL1-TR003098 (JHU ICTR), UL1-TR001881 (UCLA CTSI), P30-AI-050409 (Atlanta CFAR), P30-AI-073961 (Miami CFAR), P30-AI-050410 (UNC CFAR), P30-AI-027767 (UAB CFAR), P30-MH-116867 (Miami CHARM), UL1-TR001409 (DC CTSA), KL2-TR001432 (DC CTSA), and TL1-TR001431 (DC CTSA). The MACS CVD2 study is funded by National Heart Lung and Blood Institute (NHLBI), R01 HL095129-01 (Wendy Post). The authors gratefully acknowledge the contributions of study participants and dedication of the staff at MWCCS sites. This work is mainly supported by the NIH R01AG062383 and the NCI supplement to the Wistar Institute Cancer Center (P30 CA010815) to M.A-M. M.A-M. is also funded by the NIH grants, R01AI165079, R01NS117458, R01DK123733, R21AI170166, Penn Center for AIDS Research (P30 AI 045008), and the NIH-funded BEAT-HIV Martin Delaney Collaboratory to cure HIV-1 infection (1UM1Al126620) as well as the Gates foundation grant # Inv-033977. Mass spectrometry based glycomic analyses was partially supported by NIH R24GM137782 and GlycoMIP, a National Science Foundation Materials Innovation Platform funded through Cooperative Agreement DMR-1933525. We Would like to thank Drs. Michel Nussenzweig, Costin Tomescu, and Luis J. Montaner for providing the wild-type 10-1074 for the glycoengineering experiments and Dr. Daniel Kulp for providing HIV-1 Env trimer, BG505. Data in this manuscript were collected by the MACS/WIHS Combined Cohort Study (MWCCS). The contents of this publication are solely the responsibility of the authors and do not represent the official views of the National Institutes of Health (NIH). MWCCS (Principal Investigators): Atlanta CRS (Ighovwerha Ofotokun, Anandi Sheth, and Gina Wingood), U01-HL146241; Baltimore CRS (Todd Brown and Joseph Margolick), U01-HL146201; Bronx CRS (Kathryn Anastos, David Hanna, and Anjali Sharma), U01-HL146204; Brooklyn CRS (Deborah Gustafson and Tracey Wilson), U01-HL146202; Data Analysis and Coordination Center (Gypsyamber D\u2019Souza, Stephen Gange and Elizabeth Topper), U01-HL146193; Chicago-Cook County CRS (Mardge Cohen and Audrey French), U01-HL146245; Chicago-Northwestern CRS (Steven Wolinsky, Frank Palella, and Valentina Stosor), U01-HL146240; Northern California CRS (Bradley Aouizerat, Jennifer Price, and Phyllis Tien), U01-HL146242; Los Angeles CRS (Roger Detels and Matthew Mimiaga), U01-HL146333; Metropolitan Washington CRS (Seble Kassaye and Daniel Merenstein), U01-HL146205; Miami CRS (Maria Alcaide, Margaret Fischl, and Deborah Jones), U01-HL146203; Pittsburgh CRS (Jeremy Martinson and Charles Rinaldo), U01-HL146208; UAB-MS CRS (Mirjam-Colette Kempf, Jodie Dionne-Odom, Deborah Konkle-Parker, and James B. Brock), U01-HL146192; UNC CRS (Adaora Adimora and Michelle Floris-Moore), U01-HL146194. The MWCCS is funded primarily by the National Heart, Lung, and Blood Institute (NHLBI), with additional co-funding from the Eunice Kennedy Shriver National Institute Of Child Health & Human Development (NICHD), National Institute On Aging (NIA), National Institute Of Dental & Craniofacial Research (NIDCR), National Institute Of Allergy And Infectious Diseases (NIAID), National Institute Of Neurological Disorders And Stroke (NINDS), National Institute Of Mental Health (NIMH), National Institute On Drug Abuse (NIDA), National Institute Of Nursing Research (NINR), National Cancer Institute (NCI), National Institute on Alcohol Abuse and Alcoholism (NIAAA), National Institute on Deafness and Other Communication Disorders (NIDCD), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute on Minority Health and Health Disparities (NIMHD), and in coordination and alignment with the research priorities of the National Institutes of Health, Office of AIDS Research (OAR). MWCCS data collection is also supported by UL1-TR000004 (UCSF CTSA), UL1-TR003098 (JHU ICTR), UL1-TR001881 (UCLA CTSI), P30-AI-050409 (Atlanta CFAR), P30-AI-073961 (Miami CFAR), P30-AI-050410 (UNC CFAR), P30-AI-027767 (UAB CFAR), P30-MH-116867 (Miami CHARM), UL1-TR001409 (DC CTSA), KL2-TR001432 (DC CTSA), and TL1-TR001431 (DC CTSA). The MACS CVD2 study is funded by National Heart Lung and Blood Institute (NHLBI), R01 HL095129-01 (Wendy Post). The authors gratefully acknowledge the contributions of study participants and dedication of the staff at MWCCS sites.

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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10.1038/s41467-024-47279-4

Cite this

Giron, L. B., Liu, Q., Adeniji, O. S., Yin, X., Kannan, T., Ding, J., Lu, D. Y., Langan, S., Zhang, J., Azevedo, J. L. L. C., Li, S. H., Shalygin, S., Azadi, P., Hanna, D. B., Ofotokun, I., Lazar, J., Fischl, M. A., Haberlen, S., Macatangay, B., ... Abdel-Mohsen, M. (2024). Immunoglobulin G N-glycan markers of accelerated biological aging during chronic HIV infection. Nature communications, 15(1), Article 3035. https://doi.org/10.1038/s41467-024-47279-4

@article{4dfd06b692e749bfa650b11f0ba0f218,

title = "Immunoglobulin G N-glycan markers of accelerated biological aging during chronic HIV infection",

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.",

author = "Giron, \{Leila B.\} and Qin Liu and Adeniji, \{Opeyemi S.\} and Xiangfan Yin and Toshitha Kannan and Jianyi Ding and Lu, \{David Y.\} and Susan Langan and Jinbing Zhang and Azevedo, \{Joao L.L.C.\} and Li, \{Shuk Hang\} and Sergei Shalygin and Parastoo Azadi and Hanna, \{David B.\} and Igho Ofotokun and Jason Lazar and Fischl, \{Margaret A.\} and Sabina Haberlen and Bernard Macatangay and Adimora, \{Adaora A.\} and Jamieson, \{Beth D.\} and Charles Rinaldo and Daniel Merenstein and Roan, \{Nadia R.\} and Olaf Kutsch and Stephen Gange and Wolinsky, \{Steven M.\} and Witt, \{Mallory D.\} and Post, \{Wendy S.\} and Andrew Kossenkov and Landay, \{Alan L.\} and Ian Frank and Tien, \{Phyllis C.\} and Robert Gross and Brown, \{Todd T.\} and Mohamed Abdel-Mohsen",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2024.",

year = "2024",

month = dec,

doi = "10.1038/s41467-024-47279-4",

language = "English (US)",

volume = "15",

journal = "Nature communications",

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Giron, LB, Liu, Q, Adeniji, OS, Yin, X, Kannan, T, Ding, J, Lu, DY, Langan, S, Zhang, J, Azevedo, JLLC, Li, SH, Shalygin, S, Azadi, P, Hanna, DB, Ofotokun, I, Lazar, J, Fischl, MA, Haberlen, S, Macatangay, B, Adimora, AA, Jamieson, BD, Rinaldo, C, Merenstein, D, Roan, NR, Kutsch, O, Gange, S, Wolinsky, SM, Witt, MD, Post, WS, Kossenkov, A, Landay, AL, Frank, I, Tien, PC, Gross, R, Brown, TT & Abdel-Mohsen, M 2024, 'Immunoglobulin G N-glycan markers of accelerated biological aging during chronic HIV infection', Nature communications, vol. 15, no. 1, 3035. https://doi.org/10.1038/s41467-024-47279-4

TY - JOUR

T1 - Immunoglobulin G N-glycan markers of accelerated biological aging during chronic HIV infection

AU - Giron, Leila B.

AU - Liu, Qin

AU - Adeniji, Opeyemi S.

AU - Yin, Xiangfan

AU - Kannan, Toshitha

AU - Ding, Jianyi

AU - Lu, David Y.

AU - Langan, Susan

AU - Zhang, Jinbing

AU - Azevedo, Joao L.L.C.

AU - Li, Shuk Hang

AU - Shalygin, Sergei

AU - Azadi, Parastoo

AU - Hanna, David B.

AU - Ofotokun, Igho

AU - Lazar, Jason

AU - Fischl, Margaret A.

AU - Haberlen, Sabina

AU - Macatangay, Bernard

AU - Adimora, Adaora A.

AU - Jamieson, Beth D.

AU - Rinaldo, Charles

AU - Merenstein, Daniel

AU - Roan, Nadia R.

AU - Kutsch, Olaf

AU - Gange, Stephen

AU - Wolinsky, Steven M.

AU - Witt, Mallory D.

AU - Post, Wendy S.

AU - Kossenkov, Andrew

AU - Landay, Alan L.

AU - Frank, Ian

AU - Tien, Phyllis C.

AU - Gross, Robert

AU - Brown, Todd T.

AU - Abdel-Mohsen, Mohamed

PY - 2024/12

Y1 - 2024/12

N2 - 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.

AB - 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.

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JF - Nature communications

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Immunoglobulin G N-glycan markers of accelerated biological aging during chronic HIV infection

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