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Identification of lipocalin and apolipoprotein A1 as biomarkers of chronic obstructive pulmonary disease

Nicholas, Benjamin L., Skipp, Paul, Barton, Sheila, Singh, Dave, Bagmane, Dinesh, Mould, Richard, Angco, Gilbert, Ward, Jon, Guha-Niyogi, Binita, Wilson, Susan, Howarth, Peter, Davies, Donna E., Rennard, Stephen, O'Connor, C. David and Djukanovic, Ratko (2010) Identification of lipocalin and apolipoprotein A1 as biomarkers of chronic obstructive pulmonary disease American Journal of Respiratory and Critical Care Medicine, 181, (10), pp. 1049-1060. (doi:10.1164/rccm.200906-0857OC).

Record type: Article

Abstract

Rationale: much effort is being made to discover non-invasive biomarkers of chronic airways disease that might enable better management, predict prognosis and provide new therapeutic targets.

Objectives: to undertake a comprehensive, unbiased proteomic analysis of induced sputum and identify novel non-invasive biomarkers for chronic obstructive pulmonary disease (COPD). Methods: Induced sputum was obtained from COPD patients with a spectrum of disease severity and control subjects. Two-dimensional gel electrophoresis and mass spectrometric identification of differentially expressed proteins was first applied to induced sputum from GOLD Stage 2 COPD patients and healthy smoker control subjects. Initial results thus obtained were validated by a combination of immunoassays (Western blotting and ELISA) applied to a large subject cohort. The biomarkers were localised to bronchial mucosa by immunohistochemistry.

Measurements and main results: of 1325 individual protein spots identified, 37 were quantitatively and 3 qualitatively different between the two groups (p<0.05%). 40 protein spots were subjected to tandem mass spectrometry, which identified 15 separate protein species. Seven of these were further quantified in induced sputum from 97 individuals. Using this sequential approach, two of these potential biomarkers (apolipoprotein A1 and lipocalin-1) were found to be significantly reduced in COPD patients when compared to healthy smokers. Their levels correlated with FEV1/FVC, indicating their relationship to disease severity.

Conclusions: a potential role for apolipoprotein A1 and lipocalin-1 in innate defence has been postulated previously; our discovery of their reduction in COPD indicates a deficient innate defence system in airways disease that could explain increased susceptibility to infectious exacerbations

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More information

Published date: 15 May 2010
Keywords: 2d page, induced sputum, proteome, biomarkers, copd
Organisations: Infection Inflammation & Immunity, Biological Sciences

Identifiers

Local EPrints ID: 72759
URI: http://eprints.soton.ac.uk/id/eprint/72759
ISSN: 1073-449X
PURE UUID: ec147071-c009-478c-b10e-4c710acc59b8
ORCID for Paul Skipp: ORCID iD orcid.org/0000-0002-2995-2959
ORCID for Sheila Barton: ORCID iD orcid.org/0000-0003-4963-4242
ORCID for Ratko Djukanovic: ORCID iD orcid.org/0000-0001-6039-5612

Catalogue record

Date deposited: 23 Feb 2010
Last modified: 18 Jul 2017 23:53

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Contributors

Author: Benjamin L. Nicholas
Author: Paul Skipp ORCID iD
Author: Sheila Barton ORCID iD
Author: Dave Singh
Author: Dinesh Bagmane
Author: Richard Mould
Author: Gilbert Angco
Author: Jon Ward
Author: Binita Guha-Niyogi
Author: Susan Wilson
Author: Peter Howarth
Author: Donna E. Davies
Author: Stephen Rennard
Author: C. David O'Connor

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