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

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Title: IL-17-high asthma with features of a psoriasis immunophenotype
Authors: Östling, J
Van Geest, M
Schofield, JPR
Jevnikar, Z
Wilson, S
Ward, J
Lutter, R
Shaw, DE
Bakke, PS
Caruso, M
Dahlen, S-E
Fowler, SJ
Horváth, I
Krug, N
Montuschi, P
Sanak, M
Sandström, T
Sun, K
Pandis, I
Auffray, C
Sousa, AR
Guo, Y
Adcock, IM
Howarth, P
Chung, KF
Bigler, J
Sterk, PJ
Skipp, PJ
Djukanović, R
Vaarala, O
U-BIOPRED Study Group
Item Type: Journal 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.
Issue Date: Nov-2019
Date of Acceptance: 18-Mar-2019
URI: http://hdl.handle.net/10044/1/69593
DOI: 10.1016/j.jaci.2019.03.027
ISSN: 0091-6749
Publisher: Elsevier
Start Page: 1198
End Page: 1213
Journal / Book Title: Journal of Allergy and Clinical Immunology
Volume: 144
Issue: 5
Copyright Statement: © 2019 American Academy of Allergy, Asthma & Immunology. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence http://creativecommons.org/licenses/by-nc-nd/4.0/
Sponsor/Funder: Commission of the European Communities
Funder's Grant Number: 115010
Keywords: Science & Technology
Life Sciences & Biomedicine
Allergy
Immunology
IL-17
asthma
bronchial biopsies
bronchial brushings
biomarkers
psoriasis
URINARY-EXCRETION
DOUBLE-BLIND
EXPRESSION
CELLS
EXACERBATION
INFLAMMATION
POPULATION
BRODALUMAB
PHENOTYPES
ENDOTYPES
IL-17
asthma
biomarkers
bronchial biopsies
bronchial brushings
psoriasis
U-BIOPRED Study Group
Interleukin-17
asthma
biomarkers
bronchial biopsies
bronchial brushings
psoriasis
1107 Immunology
Allergy
Publication Status: Published
Conference Place: United States
Online Publication Date: 2019-04-15
Appears in Collections:Computing
National Heart and Lung Institute
Faculty of Engineering