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

Epidemiology & Population Health

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

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

ASJC Scopus subject areas

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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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

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

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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",

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

language = "English (US)",

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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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VL - 15

JO - Nature communications

JF - Nature communications

IS - 1

M1 - 3035

ER -

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

Abstract

ASJC Scopus subject areas

UN SDGs

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