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 po...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-04-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-47279-4 |
| _version_ | 1797209216608370688 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Leila B. Giron |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-24T09:51:11Z |
| format | Article |
| id | doaj.art-834ccc7d78f64593bd700f4fd920f417 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-04-24T09:51:11Z |
| publishDate | 2024-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-834ccc7d78f64593bd700f4fd920f4172024-04-14T11:22:24ZengNature PortfolioNature Communications2041-17232024-04-0115112310.1038/s41467-024-47279-4Immunoglobulin G N-glycan markers of accelerated biological aging during chronic HIV infectionLeila B. Giron0Qin Liu1Opeyemi S. Adeniji2Xiangfan Yin3Toshitha Kannan4Jianyi Ding5David Y. Lu6Susan Langan7Jinbing Zhang8Joao L. L. C. Azevedo9Shuk Hang Li10Sergei Shalygin11Parastoo Azadi12David B. Hanna13Igho Ofotokun14Jason Lazar15Margaret A. Fischl16Sabina Haberlen17Bernard Macatangay18Adaora A. Adimora19Beth D. Jamieson20Charles Rinaldo21Daniel Merenstein22Nadia R. Roan23Olaf Kutsch24Stephen Gange25Steven M. Wolinsky26Mallory D. Witt27Wendy S. Post28Andrew Kossenkov29Alan L. Landay30Ian Frank31Phyllis C. Tien32Robert Gross33Todd T. Brown34Mohamed Abdel-Mohsen35The Wistar InstituteThe Wistar InstituteThe Wistar InstituteThe Wistar InstituteThe Wistar InstituteThe Wistar InstituteThe Wistar InstituteJohns Hopkins UniversityJohns Hopkins UniversityThe Wistar InstituteUniversity of Pennsylvania Perelman School of MedicineUniversity of GeorgiaUniversity of GeorgiaAlbert Einstein College of MedicineDivision of Infectious Diseases, Department of Medicine, Emory University School of MedicineSUNY Downstate Health Sciences UniversityDivision of Infectious Disease, Department of Medicine, University of MiamiJohns Hopkins UniversityUniversity of PittsburghUniversity of North CarolinaUniversity of California, Los AngelesUniversity of PittsburghGeorgetown University Medical CenterGladstone InstitutesUniversity of Alabama at BirminghamJohns Hopkins UniversityNorthwestern UniversityLundquist Institute of Biomedical Research at Harbor-UCLA Medical CenterJohns Hopkins UniversityThe Wistar InstituteRush UniversityUniversity of Pennsylvania Perelman School of MedicineUniversity of California San FranciscoUniversity of Pennsylvania Perelman School of MedicineJohns Hopkins UniversityThe Wistar InstituteAbstract 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.https://doi.org/10.1038/s41467-024-47279-4 |
| spellingShingle | 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 Immunoglobulin G N-glycan markers of accelerated biological aging during chronic HIV infection Nature Communications |
| title | Immunoglobulin G N-glycan markers of accelerated biological aging during chronic HIV infection |
| title_full | Immunoglobulin G N-glycan markers of accelerated biological aging during chronic HIV infection |
| title_fullStr | Immunoglobulin G N-glycan markers of accelerated biological aging during chronic HIV infection |
| title_full_unstemmed | Immunoglobulin G N-glycan markers of accelerated biological aging during chronic HIV infection |
| title_short | Immunoglobulin G N-glycan markers of accelerated biological aging during chronic HIV infection |
| title_sort | immunoglobulin g n glycan markers of accelerated biological aging during chronic hiv infection |
| url | https://doi.org/10.1038/s41467-024-47279-4 |
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