Abstract
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.
Objectives 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 (BALF) 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 (FEV1pp). We adjusted for multiple comparisons using a false discovery rate (FDR) adjustment. Significant proteins were entered into a pathway overrepresentation 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 FEV1pp 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 PWH and decreased lung function (FEV1pp). Pathway analysis reveals cell adhesion molecules having potentially important roles in this process.
Footnotes
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Conflict of interest: Chris H. Wendt reports support for the present manuscript from National Institutes of Health grant R01 HL140971-01A1. Support for attending meetings and/or travel from National Institutes of Health grant R01 HL140971-01A, outside the submitted work; Participation on Data and Safety Monitoring Board for the Alpha1 Biomarkers Consortium, NIH, outside the submitted work.
Conflict of interest: Danielle Weise reports support for the present manuscript from National Institutes of Health grant R01 HL140971-01A1. Support for attending meetings and/or travel from National Institutes of Health grant R01 HL140971-01A, outside the submitted work.
Conflict of interest: Eric F. Lock reports support for the present manuscript from National Institutes of Health grant R01 HL140971-01A1.
Conflict of interest: Laurie Parker reports support for the present manuscript from National Institutes of Health grant R01 HL140971-01A1.
Conflict of interest: Pratik Jagtap reports support for the present manuscript from National Institutes of Health grant R01 HL140971-01A1.
Conflict of interest: Sarah Samorodnitsky reports support for the present manuscript from National Institutes of Health grant R01 HL140971-01A1.
Conflict of interest: Monica Kruk reports support for the present manuscript from National Institutes of Health grant R01 HL140971-01A1. Support for attending meetings and/or travel from National Institutes of Health grant R01 HL140971-01A, outside the submitted work.
Conflict of interest: Janice Leung reports support for the present manuscript from Canadian Institutes of Health Research, and BC Lung Foundation. Grants or contracts from Canadian Institutes of Health Research, and BC Lung Foundation, outside the submitted work; Payment received from BC Lung Foundation for patient forums, outside the submitted work; Payment received from University of British Columbia for education lectures, outside the submitted work; Participation in Enhance Quality Safety, and Patient experience in Chronic Obstructive Pulmonary Disorder (EQuiP COPD) Data and Safety Monitoring Board, outside the submitted work; Member of the steering committee for Canadian Respiratory Research Network, and CanCOLD Study, outside the submitted work.
Conflict of interest: Ken Kunisaki reports support for the present manuscript from National Institutes of Health grant R01 HL140971-01A1. Consulting fees from Allergan, outside the submitted work; Participation in Data Safety Monitoring Board for Nuvaira, and Organicell, outside the submitted work; Volunteer for American Thoracic Society Proposal Review Committee, outside the submitted work.
Conflict of interest: Timothy Griffin reports support for the present manuscript from National Institutes of Health grant R01 HL140971-01A1.
Conflict of interest: Alison Morris reports support for the present manuscript from National Institutes of Health grant R01 HL140971-01A1.
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- Received March 4, 2024.
- Accepted September 12, 2024.
- Copyright ©The authors 2024
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