Plasma protein signatures of adult asthma.

Autor: Smilnak GJ; Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA., Lee Y; Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, Texas, USA., Chattopadhyay A; Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA., Wyss AB; Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA., White JD; Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA.; GenOmics and Translational Research Center, Biostatistics and Epidemiology Division, RTI International, Research Triangle Park, North Carolina, USA., Sikdar S; Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA.; Department of Mathematics and Statistics, Old Dominion University, Norfolk, Virginia, USA., Jin J; Westat, Inc., Durham, North Carolina, USA., Grant AJ; MRC Biostatistics Unit, University of Cambridge, Cambridge, UK., Motsinger-Reif AA; Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA., Li JL; Integrative Bioinformatics Support Group, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA., Lee M; Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA., Yu B; Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, Texas, USA., London SJ; Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina, USA.
Jazyk: angličtina
Zdroj: Allergy [Allergy] 2024 Mar; Vol. 79 (3), pp. 643-655. Date of Electronic Publication: 2024 Jan 23.
DOI: 10.1111/all.16000
Abstrakt: Background: Adult asthma is complex and incompletely understood. Plasma proteomics is an evolving technique that can both generate biomarkers and provide insights into disease mechanisms. We aimed to identify plasma proteomic signatures of adult asthma.
Methods: Protein abundance in plasma was measured in individuals from the Agricultural Lung Health Study (ALHS) (761 asthma, 1095 non-case) and the Atherosclerosis Risk in Communities study (470 asthma, 10,669 non-case) using the SOMAScan 5K array. Associations with asthma were estimated using covariate adjusted logistic regression and meta-analyzed using inverse-variance weighting. Additionally, in ALHS, we examined phenotypes based on both asthma and seroatopy (asthma with atopy (n = 207), asthma without atopy (n = 554), atopy without asthma (n = 147), compared to neither (n = 948)).
Results: Meta-analysis of 4860 proteins identified 115 significantly (FDR<0.05) associated with asthma. Multiple signaling pathways related to airway inflammation and pulmonary injury were enriched (FDR<0.05) among these proteins. A proteomic score generated using machine learning provided predictive value for asthma (AUC = 0.77, 95% CI = 0.75-0.79 in training set; AUC = 0.72, 95% CI = 0.69-0.75 in validation set). Twenty proteins are targeted by approved or investigational drugs for asthma or other conditions, suggesting potential drug repurposing. The combined asthma-atopy phenotype showed significant associations with 20 proteins, including five not identified in the overall asthma analysis.
Conclusion: This first large-scale proteomics study identified over 100 plasma proteins associated with current asthma in adults. In addition to validating previous associations, we identified many novel proteins that could inform development of diagnostic biomarkers and therapeutic targets in asthma management.
(© 2024 The Authors. Allergy published by John Wiley & Sons Ltd and European Academy of Allergy and Clinical Immunology. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)
Databáze: MEDLINE
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