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IL-17-high asthma with features of a psoriasis immunophenotype

IL-17-high asthma with features of a psoriasis immunophenotype
IL-17-high asthma with features of a psoriasis immunophenotype
Background: the role of interleukin-17 immunity is well established in inflammatory diseases like psoriasis and inflammatory bowel disease but not in asthma where further study is required.

Objective: to undertake a deep-phenotyping study of asthmatics with up-regulated interleukin-17 immunity.

Methods: whole genome transcriptomic analysis was performed using epithelial brushings, bronchial biopsies (91 asthmatics patients and 46 healthy controls) and whole blood samples (n=498) from the U-BIOPRED cohort. Gene signatures induced in vitro by interleukin-17 and interleukin-13 in bronchial epithelial cells were used to identify patients with interleukin-17-high and interleukin-13-high phenotypes of asthma.

Results: 22 out of 91 patients were identified with interleukin-17 and 9 patients with interleukin-13 gene signatures. The interleukin-17-high asthmatics were characterised by risk of frequent exacerbations, airway (sputum and mucosal) neutrophilia, decreased lung microbiota diversity and urinary biomarker evidence of activation of the thromboxane B2 pathway. In pathway analysis, the differentially expressed genes in interleukin-17-high patients were shared with those reported as altered in psoriasis lesions, and included genes regulating epithelial barrier function and defence mechanisms, such as interleukin-1β, interleukin-6, interleukin-8, and beta-defensin.

Conclusion: the interleukin-17-high asthma phenotype, characterized by bronchial epithelial dysfunction, upregulated anti-microbial and inflammatory response, resembles the immunophenotype of psoriasis, including activation of the thromboxane B2 pathway which should be considered as a biomarker for this phenotype in further studies, including clinical trials targeting interleukin-17.
Interleukin-17, asthma, bronchial biopsies, bronchial brushings, biomarkers, psoriasis
0091-6749
1198-1213
Östling, Jörgen
98f5fad2-945e-4061-8791-3c89946fb821
van Geest, Marleen
419a034e-3039-4dc1-876f-0679c52901ab
Schofield, James
b6d3a808-50ac-4365-bc0d-80da333a4ae7
Skipp, Paul
1ba7dcf6-9fe7-4b5c-a9d0-e32ed7f42aa5
Djukanovic, Ratko
d9a45ee7-6a80-4d84-a0ed-10962660a98d
Wilson, Susan
21c6875d-6870-441b-ae7a-603562a646b8
Howarth, Peter
ff19c8c4-86b0-4a88-8f76-b3d87f142a21
U-BIOPRED Study Group
et al.
Östling, Jörgen
98f5fad2-945e-4061-8791-3c89946fb821
van Geest, Marleen
419a034e-3039-4dc1-876f-0679c52901ab
Schofield, James
b6d3a808-50ac-4365-bc0d-80da333a4ae7
Skipp, Paul
1ba7dcf6-9fe7-4b5c-a9d0-e32ed7f42aa5
Djukanovic, Ratko
d9a45ee7-6a80-4d84-a0ed-10962660a98d
Wilson, Susan
21c6875d-6870-441b-ae7a-603562a646b8
Howarth, Peter
ff19c8c4-86b0-4a88-8f76-b3d87f142a21

Östling, Jörgen, van Geest, Marleen and Schofield, James , U-BIOPRED Study Group and et al. (2019) IL-17-high asthma with features of a psoriasis immunophenotype. Journal of Allergy and Clinical Immunology, 144 (5), 1198-1213. (doi:10.1016/j.jaci.2019.03.027).

Record type: Article

Abstract

Background: the role of interleukin-17 immunity is well established in inflammatory diseases like psoriasis and inflammatory bowel disease but not in asthma where further study is required.

Objective: to undertake a deep-phenotyping study of asthmatics with up-regulated interleukin-17 immunity.

Methods: whole genome transcriptomic analysis was performed using epithelial brushings, bronchial biopsies (91 asthmatics patients and 46 healthy controls) and whole blood samples (n=498) from the U-BIOPRED cohort. Gene signatures induced in vitro by interleukin-17 and interleukin-13 in bronchial epithelial cells were used to identify patients with interleukin-17-high and interleukin-13-high phenotypes of asthma.

Results: 22 out of 91 patients were identified with interleukin-17 and 9 patients with interleukin-13 gene signatures. The interleukin-17-high asthmatics were characterised by risk of frequent exacerbations, airway (sputum and mucosal) neutrophilia, decreased lung microbiota diversity and urinary biomarker evidence of activation of the thromboxane B2 pathway. In pathway analysis, the differentially expressed genes in interleukin-17-high patients were shared with those reported as altered in psoriasis lesions, and included genes regulating epithelial barrier function and defence mechanisms, such as interleukin-1β, interleukin-6, interleukin-8, and beta-defensin.

Conclusion: the interleukin-17-high asthma phenotype, characterized by bronchial epithelial dysfunction, upregulated anti-microbial and inflammatory response, resembles the immunophenotype of psoriasis, including activation of the thromboxane B2 pathway which should be considered as a biomarker for this phenotype in further studies, including clinical trials targeting interleukin-17.

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IL-17 - Accepted Manuscript
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More information

Accepted/In Press date: 18 March 2019
e-pub ahead of print date: 15 April 2019
Published date: November 2019
Keywords: Interleukin-17, asthma, bronchial biopsies, bronchial brushings, biomarkers, psoriasis

Identifiers

Local EPrints ID: 430413
URI: http://eprints.soton.ac.uk/id/eprint/430413
ISSN: 0091-6749
PURE UUID: efef4316-2fd4-46c1-8fd6-a882f9d03269
ORCID for Paul Skipp: ORCID iD orcid.org/0000-0002-2995-2959
ORCID for Ratko Djukanovic: ORCID iD orcid.org/0000-0001-6039-5612
ORCID for Susan Wilson: ORCID iD orcid.org/0000-0003-1305-8271

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Date deposited: 30 Apr 2019 16:30
Last modified: 22 Oct 2021 04:02

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