Lung proteome and metabolome endotype in HIV-associated obstructive lung disease

Sarah Samorodnitsky, Eric F. Lock, Monica Kruk, Alison Morris, Janice M. Leung, Ken M. Kunisaki, Timothy J. Griffin, Chris H. Wendt

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Purpose Obstructive lung disease is increasingly common among persons with HIV, both smokers and nonsmokers. We used aptamer proteomics to identify proteins and associated pathways in HIV-associated obstructive lung disease. Methods Bronchoalveolar lavage fluid (BALF) samples from 26 persons living with HIV with obstructive lung disease were matched to persons living with HIV without obstructive lung disease based on age, smoking status and antiretroviral treatment. 6414 proteins were measured using SomaScan® aptamer-based assay. We used sparse distance-weighted discrimination (sDWD) to test for a difference in protein expression and permutation tests to identify univariate associations between proteins and forced expiratory volume in 1 s % predicted (FEV1 % pred). Significant proteins were entered into a pathway over-representation analysis. We also constructed protein-driven endotypes using K-means clustering and performed over-representation analysis on the proteins that were significantly different between clusters. We compared protein-associated clusters to those obtained from BALF and plasma metabolomics data on the same patient cohort. Results After filtering, we retained 3872 proteins for further analysis. Based on sDWD, protein expression was able to separate cases and controls. We found 575 proteins that were significantly correlated with FEV1 % pred after multiple comparisons adjustment. We identified two protein-driven endotypes, one of which was associated with poor lung function, and found that insulin and apoptosis pathways were differentially represented. We found similar clusters driven by metabolomics in BALF but not plasma. Conclusion Protein expression differs in persons living with HIV with and without obstructive lung disease. We were not able to identify specific pathways differentially expressed among patients based on FEV1 % pred; however, we identified a unique protein endotype associated with insulin and apoptotic pathways.

Original languageEnglish (US)
Article number00332-2022
JournalERJ Open Research
Issue number2
StatePublished - Mar 1 2023

Bibliographical note

Funding Information:
Support statement: Supported by National Institutes of Health grant R01 HL140971-01A1 (all authors). This material is also the result of work supported with resources and the use of facilities at the Minneapolis Veterans Affairs Medical Center, Minneapolis, MN, USA. The views expressed in this article are those of the authors and do not reflect the views of the US Government, the Department of Veterans Affairs, the funders, the sponsors or any of the authors’ affiliated academic institutions. Funding information for this article has been deposited with the Crossref Funder Registry.

Publisher Copyright:
© The authors 2023.

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