The lung proteome in HIV-associated obstructive lung disease
Rationale Obstructive lung disease is increasingly common among persons living with HIV (PLWH). There are currently no validated biomarkers that identify individuals at risk of developing obstructive lung disease (OLD), and specific mechanisms contributing to HIV-associated OLD remain elusive, indep...
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| Format: | Article |
| Language: | English |
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European Respiratory Society
2025-03-01
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| Series: | ERJ Open Research |
| Online Access: | http://openres.ersjournals.com/content/11/2/00204-2024.full |
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| author | Sarah Samorodnitsky Danielle Weise Eric F. Lock Ken M. Kunisaki Alison Morris Janice M. Leung Monica Kruk Laurie Parker Pratik Jagtap Timothy J. Griffin Chris H. Wendt |
| author_facet | Sarah Samorodnitsky Danielle Weise Eric F. Lock Ken M. Kunisaki Alison Morris Janice M. Leung Monica Kruk Laurie Parker Pratik Jagtap Timothy J. Griffin Chris H. Wendt |
| author_sort | Sarah Samorodnitsky |
| collection | DOAJ |
| description | Rationale
Obstructive lung disease is increasingly common among persons living with HIV (PLWH). There are currently no validated biomarkers that identify individuals at risk of developing obstructive lung disease (OLD), and specific mechanisms contributing to HIV-associated OLD remain elusive, independent of smoking. We sought to identify biomarkers and biological pathways associated with OLD using a broad proteomic approach.
Methods
We performed tandem mass tagging and mass spectrometry (MS) analysis on bronchoalveolar lavage fluid samples from persons living with HIV with OLD (n=26) and without OLD (n=26). We combined untargeted MS with a targeted SomaScan aptamer-based approach. We used Pearson correlation tests to identify associations between each protein and lung function (forced expiratory volume in 1 s (FEV1) % pred). We adjusted for multiple comparisons using a false discovery rate adjustment. Significant proteins were entered into a pathway over-representation analysis. Protein-driven endotypes were constructed using K-means clustering.
Measurements and main results
We identified over 3800 proteins by MS and identified 254 proteins that correlated with FEV1 % pred when we combined the MS and SomaScan proteomes when adjusting for smoking status. Pathway analysis revealed cell adhesion molecules as significant.
Conclusions
Protein expression differs in the lung of PLWH and decreased lung function (FEV1 % pred). Pathway analysis reveals cell adhesion molecules having potentially important roles in this process. |
| format | Article |
| id | doaj-art-f9d0310aa0a84f6da531868adcb9b51b |
| institution | DOAJ |
| issn | 2312-0541 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | European Respiratory Society |
| record_format | Article |
| series | ERJ Open Research |
| spelling | doaj-art-f9d0310aa0a84f6da531868adcb9b51b2025-08-20T03:11:29ZengEuropean Respiratory SocietyERJ Open Research2312-05412025-03-0111210.1183/23120541.00204-202400204-2024The lung proteome in HIV-associated obstructive lung diseaseSarah Samorodnitsky0Danielle Weise1Eric F. Lock2Ken M. Kunisaki3Alison Morris4Janice M. Leung5Monica Kruk6Laurie Parker7Pratik Jagtap8Timothy J. Griffin9Chris H. Wendt10 Biostatistics Division, School of Public Health, University of Minnesota, Minneapolis, MN, USA Department of Medicine, University of Minnesota, Minneapolis, MN, USA Biostatistics Division, School of Public Health, University of Minnesota, Minneapolis, MN, USA Department of Medicine, University of Minnesota, Minneapolis, MN, USA Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Department of Medicine, University of British Columbia, Vancouver, Canada Department of Medicine, University of Minnesota, Minneapolis, MN, USA Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA Department of Medicine, University of Minnesota, Minneapolis, MN, USA Rationale Obstructive lung disease is increasingly common among persons living with HIV (PLWH). There are currently no validated biomarkers that identify individuals at risk of developing obstructive lung disease (OLD), and specific mechanisms contributing to HIV-associated OLD remain elusive, independent of smoking. We sought to identify biomarkers and biological pathways associated with OLD using a broad proteomic approach. Methods We performed tandem mass tagging and mass spectrometry (MS) analysis on bronchoalveolar lavage fluid samples from persons living with HIV with OLD (n=26) and without OLD (n=26). We combined untargeted MS with a targeted SomaScan aptamer-based approach. We used Pearson correlation tests to identify associations between each protein and lung function (forced expiratory volume in 1 s (FEV1) % pred). We adjusted for multiple comparisons using a false discovery rate adjustment. Significant proteins were entered into a pathway over-representation analysis. Protein-driven endotypes were constructed using K-means clustering. Measurements and main results We identified over 3800 proteins by MS and identified 254 proteins that correlated with FEV1 % pred when we combined the MS and SomaScan proteomes when adjusting for smoking status. Pathway analysis revealed cell adhesion molecules as significant. Conclusions Protein expression differs in the lung of PLWH and decreased lung function (FEV1 % pred). Pathway analysis reveals cell adhesion molecules having potentially important roles in this process.http://openres.ersjournals.com/content/11/2/00204-2024.full |
| spellingShingle | Sarah Samorodnitsky Danielle Weise Eric F. Lock Ken M. Kunisaki Alison Morris Janice M. Leung Monica Kruk Laurie Parker Pratik Jagtap Timothy J. Griffin Chris H. Wendt The lung proteome in HIV-associated obstructive lung disease ERJ Open Research |
| title | The lung proteome in HIV-associated obstructive lung disease |
| title_full | The lung proteome in HIV-associated obstructive lung disease |
| title_fullStr | The lung proteome in HIV-associated obstructive lung disease |
| title_full_unstemmed | The lung proteome in HIV-associated obstructive lung disease |
| title_short | The lung proteome in HIV-associated obstructive lung disease |
| title_sort | lung proteome in hiv associated obstructive lung disease |
| url | http://openres.ersjournals.com/content/11/2/00204-2024.full |
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