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High-throughput proteomic analysis reveals systemic dysregulation in virally suppressed people living with HIV
BACKGROUND: People living with HIV (PLHIV) receiving antiretroviral therapy (ART) exhibit persistent immune dysregulation and microbial dysbiosis, leading to development of cardiovascular diseases (CVDs). We initially compared plasma proteomic profiles between 205 PLHIV and 120 healthy control parti...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Clinical Investigation
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10393229/ https://www.ncbi.nlm.nih.gov/pubmed/37079385 http://dx.doi.org/10.1172/jci.insight.166166 |
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author | Vadaq, Nadira Zhang, Yue Vos, Wilhelm A.J.W. Groenendijk, Albert L. Blaauw, Martinus J.T. van Eekeren, Louise E. Jacobs-Cleophas, Maartje van de Wijer, Lisa dos Santos, Jéssica Cristina Gasem, Muhammad Hussein Joosten, Leo A.B. Netea, Mihai G. de Mast, Quirijn Fu, Jingyuan van der Ven, André J.A.M. Matzaraki, Vasiliki |
author_facet | Vadaq, Nadira Zhang, Yue Vos, Wilhelm A.J.W. Groenendijk, Albert L. Blaauw, Martinus J.T. van Eekeren, Louise E. Jacobs-Cleophas, Maartje van de Wijer, Lisa dos Santos, Jéssica Cristina Gasem, Muhammad Hussein Joosten, Leo A.B. Netea, Mihai G. de Mast, Quirijn Fu, Jingyuan van der Ven, André J.A.M. Matzaraki, Vasiliki |
author_sort | Vadaq, Nadira |
collection | PubMed |
description | BACKGROUND: People living with HIV (PLHIV) receiving antiretroviral therapy (ART) exhibit persistent immune dysregulation and microbial dysbiosis, leading to development of cardiovascular diseases (CVDs). We initially compared plasma proteomic profiles between 205 PLHIV and 120 healthy control participants (HCs) and validated the results in an independent cohort of 639 PLHIV and 99 HCs. Differentially expressed proteins (DEPs) were then associated to microbiome data. Finally, we assessed which proteins were linked with CVD development in PLHIV. METHODS: Proximity extension assay technology was used to measure 1,472 plasma proteins. Markers of systemic inflammation (C-reactive protein, D-dimer, IL-6, soluble CD14, and soluble CD163) and microbial translocation (IFABP) were measured by ELISA, and gut bacterial species were identified using shotgun metagenomic sequencing. Baseline CVD data were available for all PLHIV, and 205 PLHIV were recorded for development of CVD during a 5-year follow-up. RESULTS: PLHIV receiving ART had systemic dysregulation of protein concentrations, compared with HCs. Most of the DEPs originated from the intestine and lymphoid tissues and were enriched in immune- and lipid metabolism–related pathways. DEPs originating from the intestine were associated with specific gut bacterial species. Finally, we identified upregulated proteins in PLHIV (GDF15, PLAUR, RELT, NEFL, COL6A3, and EDA2R), unlike most markers of systemic inflammation, associated with the presence and risk of developing CVD during 5-year follow-up. CONCLUSION: Our findings suggest a systemic dysregulation of protein concentrations in PLHIV; some proteins were associated with CVD development. Most DEPs originated from the gut and were related to specific gut bacterial species. TRIAL REGISTRATION: ClinicalTrials.gov NCT03994835. FUNDING: AIDS-fonds (P-29001), ViiV healthcare grant (A18-1052), Spinoza Prize (NWO SPI94-212), European Research Council (ERC) Advanced grant (grant 833247), and Indonesia Endowment Fund for Education. |
format | Online Article Text |
id | pubmed-10393229 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Society for Clinical Investigation |
record_format | MEDLINE/PubMed |
spelling | pubmed-103932292023-08-02 High-throughput proteomic analysis reveals systemic dysregulation in virally suppressed people living with HIV Vadaq, Nadira Zhang, Yue Vos, Wilhelm A.J.W. Groenendijk, Albert L. Blaauw, Martinus J.T. van Eekeren, Louise E. Jacobs-Cleophas, Maartje van de Wijer, Lisa dos Santos, Jéssica Cristina Gasem, Muhammad Hussein Joosten, Leo A.B. Netea, Mihai G. de Mast, Quirijn Fu, Jingyuan van der Ven, André J.A.M. Matzaraki, Vasiliki JCI Insight Clinical Medicine BACKGROUND: People living with HIV (PLHIV) receiving antiretroviral therapy (ART) exhibit persistent immune dysregulation and microbial dysbiosis, leading to development of cardiovascular diseases (CVDs). We initially compared plasma proteomic profiles between 205 PLHIV and 120 healthy control participants (HCs) and validated the results in an independent cohort of 639 PLHIV and 99 HCs. Differentially expressed proteins (DEPs) were then associated to microbiome data. Finally, we assessed which proteins were linked with CVD development in PLHIV. METHODS: Proximity extension assay technology was used to measure 1,472 plasma proteins. Markers of systemic inflammation (C-reactive protein, D-dimer, IL-6, soluble CD14, and soluble CD163) and microbial translocation (IFABP) were measured by ELISA, and gut bacterial species were identified using shotgun metagenomic sequencing. Baseline CVD data were available for all PLHIV, and 205 PLHIV were recorded for development of CVD during a 5-year follow-up. RESULTS: PLHIV receiving ART had systemic dysregulation of protein concentrations, compared with HCs. Most of the DEPs originated from the intestine and lymphoid tissues and were enriched in immune- and lipid metabolism–related pathways. DEPs originating from the intestine were associated with specific gut bacterial species. Finally, we identified upregulated proteins in PLHIV (GDF15, PLAUR, RELT, NEFL, COL6A3, and EDA2R), unlike most markers of systemic inflammation, associated with the presence and risk of developing CVD during 5-year follow-up. CONCLUSION: Our findings suggest a systemic dysregulation of protein concentrations in PLHIV; some proteins were associated with CVD development. Most DEPs originated from the gut and were related to specific gut bacterial species. TRIAL REGISTRATION: ClinicalTrials.gov NCT03994835. FUNDING: AIDS-fonds (P-29001), ViiV healthcare grant (A18-1052), Spinoza Prize (NWO SPI94-212), European Research Council (ERC) Advanced grant (grant 833247), and Indonesia Endowment Fund for Education. American Society for Clinical Investigation 2023-06-08 /pmc/articles/PMC10393229/ /pubmed/37079385 http://dx.doi.org/10.1172/jci.insight.166166 Text en © 2023 Vadaq et al. https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Clinical Medicine Vadaq, Nadira Zhang, Yue Vos, Wilhelm A.J.W. Groenendijk, Albert L. Blaauw, Martinus J.T. van Eekeren, Louise E. Jacobs-Cleophas, Maartje van de Wijer, Lisa dos Santos, Jéssica Cristina Gasem, Muhammad Hussein Joosten, Leo A.B. Netea, Mihai G. de Mast, Quirijn Fu, Jingyuan van der Ven, André J.A.M. Matzaraki, Vasiliki High-throughput proteomic analysis reveals systemic dysregulation in virally suppressed people living with HIV |
title | High-throughput proteomic analysis reveals systemic dysregulation in virally suppressed people living with HIV |
title_full | High-throughput proteomic analysis reveals systemic dysregulation in virally suppressed people living with HIV |
title_fullStr | High-throughput proteomic analysis reveals systemic dysregulation in virally suppressed people living with HIV |
title_full_unstemmed | High-throughput proteomic analysis reveals systemic dysregulation in virally suppressed people living with HIV |
title_short | High-throughput proteomic analysis reveals systemic dysregulation in virally suppressed people living with HIV |
title_sort | high-throughput proteomic analysis reveals systemic dysregulation in virally suppressed people living with hiv |
topic | Clinical Medicine |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10393229/ https://www.ncbi.nlm.nih.gov/pubmed/37079385 http://dx.doi.org/10.1172/jci.insight.166166 |
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