Elevated peptides in lung lavage fluid associated with bronchiolitis obliterans syndrome

Matthew D. Stone, Stephen B Harvey, Gary L Nelsestuen, Cavan S Reilly, Marshall I Hertz, Christine H Wendt

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Objective: The objective of this discovery-level investigation was to use mass spectrometry to identify low mass compounds in bronchoalveolar lavage fluid from lung transplant recipients that associate with bronchiolitis obliterans syndrome. Experimental Design: Bronchoalveolar lavage fluid samples from lung transplant recipients were evaluated for small molecules using ESI-TOF mass spectrometry and correlated to the development of bronchiolitis obliterans syndrome. Peptides associated with samples from persons with bronchiolitis obliterans syndrome and controls were identified separately by MS/MS analysis. Results: The average bronchoalveolar lavage fluid MS spectrum profile of individuals that developed bronchiolitis obliterans syndrome differed greatly compared to controls. Controls demonstrated close inter-sample correlation (R = 0.97+/-0.02, average+/-SD) while bronchiolitis obliterans syndrome showed greater heterogeneity (R = 0.86+/-0.09, average+/-SD). We identified 89 features that were predictive of developing BOS grade 1 and 66 features predictive of developing BOS grade 2 or higher. Fractions from MS analysis were pooled and evaluated for peptide content. Nearly 10-fold more peptides were found in bronchiolitis obliterans syndrome relative to controls. C-terminal residues suggested trypsin-like specificity among controls compared to elastase-type enzymes among those with bronchiolitis obliterans syndrome. Conclusions: Bronchoalveolar lavage fluid from individuals with bronchiolitis obliterans syndrome has an increase in low mass components detected by mass spectrometry. Many of these features were peptides that likely result from elevated neutrophil elastase activity.

Original languageEnglish (US)
Article numbere84471
JournalPloS one
Volume9
Issue number1
DOIs
StatePublished - Jan 2 2014

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Bronchiolitis Obliterans
Bronchoalveolar Lavage Fluid
lungs
peptides
Peptides
Fluids
Mass spectrometry
Transplants
elastase
mass spectrometry
Leukocyte Elastase
Pancreatic Elastase
Mass Spectrometry
Design of experiments
Trypsin
Lung
Electrospray Ionization Mass Spectrometry
bronchiolitis
fluids
Molecules

Cite this

Elevated peptides in lung lavage fluid associated with bronchiolitis obliterans syndrome. / Stone, Matthew D.; Harvey, Stephen B; Nelsestuen, Gary L; Reilly, Cavan S; Hertz, Marshall I; Wendt, Christine H.

In: PloS one, Vol. 9, No. 1, e84471, 02.01.2014.

Research output: Contribution to journalArticle

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abstract = "Objective: The objective of this discovery-level investigation was to use mass spectrometry to identify low mass compounds in bronchoalveolar lavage fluid from lung transplant recipients that associate with bronchiolitis obliterans syndrome. Experimental Design: Bronchoalveolar lavage fluid samples from lung transplant recipients were evaluated for small molecules using ESI-TOF mass spectrometry and correlated to the development of bronchiolitis obliterans syndrome. Peptides associated with samples from persons with bronchiolitis obliterans syndrome and controls were identified separately by MS/MS analysis. Results: The average bronchoalveolar lavage fluid MS spectrum profile of individuals that developed bronchiolitis obliterans syndrome differed greatly compared to controls. Controls demonstrated close inter-sample correlation (R = 0.97+/-0.02, average+/-SD) while bronchiolitis obliterans syndrome showed greater heterogeneity (R = 0.86+/-0.09, average+/-SD). We identified 89 features that were predictive of developing BOS grade 1 and 66 features predictive of developing BOS grade 2 or higher. Fractions from MS analysis were pooled and evaluated for peptide content. Nearly 10-fold more peptides were found in bronchiolitis obliterans syndrome relative to controls. C-terminal residues suggested trypsin-like specificity among controls compared to elastase-type enzymes among those with bronchiolitis obliterans syndrome. Conclusions: Bronchoalveolar lavage fluid from individuals with bronchiolitis obliterans syndrome has an increase in low mass components detected by mass spectrometry. Many of these features were peptides that likely result from elevated neutrophil elastase activity.",
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