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Novel Application of Aptamer Proteomic Analysis in Cystic Fibrosis Bronchoalveolar Lavage Fluid.
Proteomics. Clinical Applications 2018 November 16
PURPOSE: Biomarkers are needed in cystic fibrosis (CF) to understand disease progression, assess response to therapy, and enrich enrollment for clinical trials. Aptamer-based proteomics have proven useful in blood samples. We aimed to evaluate proteins in bronchoalveolar lavage fluid (BALF) in CF children compared to controls and identify endotypes during CF exacerbations.
EXPERIMENTAL DESIGN: BALF was collected clinically from 50 patients with CF and 9 disease controls, processed, and stored per protocol. BALF supernatants were analyzed for 1129 proteins by aptamer approach (SOMAscan proteomics platform). Proteins were compared across groups and used for pathway analysis. Endotypes were identified within the CF group.
RESULTS: CF BALF had increased concentrations of neutrophil elastase, myeloperoxidase and decreased concentration of protein folding and host defense proteins. Pathways that distinguished CF subjects included interferon gamma signaling, membrane trafficking, and phospholipid metabolism. In the CF group, unbiased analysis of proteins identified two distinct endotypes that differed based on BALF white blood cell and neutrophil counts and detection of CF pathogens.
CONCLUSIONS AND CLINICAL RELEVANCE: Proteomic analysis of the CF airway demonstrates a complex environment of proteins and pathways. This work provides evidence that aptamer-based proteomics can differentiate between groups and can determine endotypes within CF. This article is protected by copyright. All rights reserved.
EXPERIMENTAL DESIGN: BALF was collected clinically from 50 patients with CF and 9 disease controls, processed, and stored per protocol. BALF supernatants were analyzed for 1129 proteins by aptamer approach (SOMAscan proteomics platform). Proteins were compared across groups and used for pathway analysis. Endotypes were identified within the CF group.
RESULTS: CF BALF had increased concentrations of neutrophil elastase, myeloperoxidase and decreased concentration of protein folding and host defense proteins. Pathways that distinguished CF subjects included interferon gamma signaling, membrane trafficking, and phospholipid metabolism. In the CF group, unbiased analysis of proteins identified two distinct endotypes that differed based on BALF white blood cell and neutrophil counts and detection of CF pathogens.
CONCLUSIONS AND CLINICAL RELEVANCE: Proteomic analysis of the CF airway demonstrates a complex environment of proteins and pathways. This work provides evidence that aptamer-based proteomics can differentiate between groups and can determine endotypes within CF. This article is protected by copyright. All rights reserved.
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