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Imaging Features of Systemic Sclerosis-Associated Interstitial Lung Disease
Published on: June 16, 2020
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The Proteomic Profile of Interstitial Lung Abnormalities
Gisli Thor Axelsson1,2, Gunnar Gudmundsson1,3, Katherine A Pratte4
1Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
American Journal of Respiratory and Critical Care Medicine
|April 19, 2022
Summary
This study identifies key blood proteins, including surfactant protein B (SFTPB), associated with early interstitial lung abnormalities (ILAs). These findings offer potential biomarkers for early detection and progression of fibrotic lung disease.
Area of Science:
- Pulmonary Medicine
- Proteomics
- Genetics
Background:
- Knowledge regarding biomarkers for interstitial lung disease (ILD) remains limited.
- Interstitial lung abnormalities (ILAs) represent radiologic findings that may indicate early stages of ILD.
Purpose of the Study:
- To identify blood proteins associated with ILAs using large-scale proteomics.
- To explore the relationship between these proteins, ILA progression, and genetic risk factors.
Main Methods:
- Utilized data from two prospective cohorts: AGES-Reykjavik (N=5,259) for discovery and COPDGene (N=4,899) for replication.
- Measured over 4,700 blood protein analytes using DNA aptamers.
- Employed regression modeling and adaptive Least Absolute Shrinkage and Selection Operator (LASSO) models for association and prediction analyses.
Main Results:
- Identified significant associations between ILAs and specific proteins, notably SFTPB, SCGB3A1, and WFDC2, which were replicated across cohorts.
- SFTPB concentrations correlated with the MUC5B promoter polymorphism (rs35705950).
- SFTPB and WFDC2 showed the strongest association with ILA progression, with predictive models achieving high areas under the receiver operating characteristic curve (0.824-0.880).
Conclusions:
- Demonstrated novel, replicated associations between blood proteins and ILAs, their progression, and genetic risk factors.
- Developed machine-learning models with significant predictive potential for ILAs.
- Highlighted several proteins as potential biomarkers for early-stage fibrotic lung disease.
