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Airway and peripheral uPAR is elevated in asthma, and identifies a severe, non-atopic subset of patients

Airway and peripheral uPAR is elevated in asthma, and identifies a severe, non-atopic subset of patients
Airway and peripheral uPAR is elevated in asthma, and identifies a severe, non-atopic subset of patients
Rationale: Genetic polymorphisms in the asthma susceptibility gene, urokinase plasminogen activator receptor (uPAR/PLAUR) have been associated with lung function decline and uPAR blood levels in asthma subjects. Preliminary studies have identified uPAR elevation in asthma; however, a definitive study regarding which clinical features of asthma uPAR may be driving is currently lacking.

Objectives: We aimed to comprehensively determine the uPAR expression profile in asthma and control subjects utilizing bronchial biopsies and serum, and to relate uPAR expression to asthma clinical features.

Methods: uPAR levels were determined in control (n = 9) and asthmatic (n = 27) bronchial biopsies using immunohistochemistry, with a semi-quantitative score defining intensity in multiple cell types. Soluble-cleaved (sc) uPAR levels were determined in serum through ELISA in UK (cases n = 129; controls n = 39) and Dutch (cases n = 514; controls n = 96) cohorts.

Measurements and main results: In bronchial tissue, uPAR was elevated in inflammatory cells in the lamina propria (P = 0.0019), bronchial epithelial (P = 0.0002) and airway smooth muscle cells (P = 0.0352) of patients with asthma, with uPAR levels correlated between the cell types. No correlation with disease severity or asthma clinical features was identified. scuPAR serum levels were elevated in patients with asthma (1.5-fold; P = 0.0008), and we identified an association between high uPAR serum levels and severe, nonatopic disease.

Conclusions: This study provides novel data that elevated airway and blood uPAR is a feature of asthma and that blood uPAR is particularly related to severe, nonatopic asthma. The findings warrant further investigation and may provide a therapeutic opportunity for this refractory population.
0105-4538
473-482
Portelli, Michael A.
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Moseley, Christopher
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Stewart, Ceri E.
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Postma, Dirkje S.
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Howarth, Peter
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Warner, Jane A.
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Holloway, John W.
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Koppelman, Gerard H.
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Brightling, Chris
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Sayers, Ian
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Portelli, Michael A.
704a16d0-d1e3-46a8-986c-cb6ef81a53f9
Moseley, Christopher
8bb94ddf-64b3-4c3b-9011-07b3706d66cd
Stewart, Ceri E.
39812638-540b-4ecf-97bf-b763c826c8b5
Postma, Dirkje S.
23c1567d-a264-48a1-9ab4-01beda374e42
Howarth, Peter
ff19c8c4-86b0-4a88-8f76-b3d87f142a21
Warner, Jane A.
8571b049-31bb-4a2a-a3c7-4184be20fe25
Holloway, John W.
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Koppelman, Gerard H.
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Brightling, Chris
a4ba69e8-3c26-42ba-9a64-2b44e93c13d0
Sayers, Ian
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Portelli, Michael A., Moseley, Christopher, Stewart, Ceri E., Postma, Dirkje S., Howarth, Peter, Warner, Jane A., Holloway, John W., Koppelman, Gerard H., Brightling, Chris and Sayers, Ian (2017) Airway and peripheral uPAR is elevated in asthma, and identifies a severe, non-atopic subset of patients. Allergy, 72 (3), 473-482. (doi:10.1111/all.13046).

Record type: Article

Abstract

Rationale: Genetic polymorphisms in the asthma susceptibility gene, urokinase plasminogen activator receptor (uPAR/PLAUR) have been associated with lung function decline and uPAR blood levels in asthma subjects. Preliminary studies have identified uPAR elevation in asthma; however, a definitive study regarding which clinical features of asthma uPAR may be driving is currently lacking.

Objectives: We aimed to comprehensively determine the uPAR expression profile in asthma and control subjects utilizing bronchial biopsies and serum, and to relate uPAR expression to asthma clinical features.

Methods: uPAR levels were determined in control (n = 9) and asthmatic (n = 27) bronchial biopsies using immunohistochemistry, with a semi-quantitative score defining intensity in multiple cell types. Soluble-cleaved (sc) uPAR levels were determined in serum through ELISA in UK (cases n = 129; controls n = 39) and Dutch (cases n = 514; controls n = 96) cohorts.

Measurements and main results: In bronchial tissue, uPAR was elevated in inflammatory cells in the lamina propria (P = 0.0019), bronchial epithelial (P = 0.0002) and airway smooth muscle cells (P = 0.0352) of patients with asthma, with uPAR levels correlated between the cell types. No correlation with disease severity or asthma clinical features was identified. scuPAR serum levels were elevated in patients with asthma (1.5-fold; P = 0.0008), and we identified an association between high uPAR serum levels and severe, nonatopic disease.

Conclusions: This study provides novel data that elevated airway and blood uPAR is a feature of asthma and that blood uPAR is particularly related to severe, nonatopic asthma. The findings warrant further investigation and may provide a therapeutic opportunity for this refractory population.

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Accepted/In Press date: 9 September 2016
e-pub ahead of print date: 5 October 2016
Published date: March 2017
Organisations: Human Development & Health, Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 401119
URI: https://eprints.soton.ac.uk/id/eprint/401119
ISSN: 0105-4538
PURE UUID: 62961d91-8e0d-4f6d-a06d-b32785c8e13b
ORCID for John W. Holloway: ORCID iD orcid.org/0000-0001-9998-0464

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Date deposited: 10 Oct 2016 10:13
Last modified: 10 Dec 2019 01:52

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Contributors

Author: Michael A. Portelli
Author: Christopher Moseley
Author: Ceri E. Stewart
Author: Dirkje S. Postma
Author: Peter Howarth
Author: Jane A. Warner
Author: Gerard H. Koppelman
Author: Chris Brightling
Author: Ian Sayers

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