Pathway discovery using transcriptomic profiles in adult-onset severe asthma

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Title: Pathway discovery using transcriptomic profiles in adult-onset severe asthma
Author(s): Hekking, PP
Loza, MJ
Pavlidis, S
De Meulder, B
Lefaudeux, D
Baribaud, F
Auffray, C
Wagener, A
Brinkman, P
Lutter, I
Bansal, A
Sousa, A
Bates, S
Pandis, Y
Fleming, L
Shaw, DE
Fowler, SJ
Guo, Y
Meiser, A
Sun, K
Corfield, J
Howarth, P
Bel, EH
Adcock, IM
Chung, KF
Djukanovic, R
Sterk, PJ
U-BIOPRED Study Group
Item Type: Journal Article
Abstract: Rationale Adult-onset severe asthma is characterized by highly symptomatic disease despite high intensity asthma treatments. Understanding of the underlying pathways of this heterogeneous disease needed for the development of targeted treatments. Gene Set Variation Analysis (GSVA) is a statistical technique to identify gene profiles in heterogeneous samples. Objective To identify gene profiles associated with adult-onset severe asthma. Methods This was a cross-sectional, observational study in which adult patients with adult-onset of asthma (defined as starting at ≥18yrs old) as compared to childhood-onset severe asthma (<18 yrs) were selected from the U-BIOPRED cohort. Gene expression was assessed on the total RNA of induced sputum (n=83), nasal brushings (n=41), and endobronchial brushings (n=65) and biopsies (n=47) (Affymetrix HT HG-U133+ PM). GSVA was used to identify differentially enriched pre-defined gene signatures of leukocyte lineage, inflammatory and induced lung injury pathways. Results Significant differentially enriched gene signatures in patients with adult-onset as compared to childhood-onset severe asthma were identified in nasal brushings (5 signatures), sputum (3 signatures) and endobronchial brushings (6 signatures). Signatures associated with eosinophilic airway inflammation, mast cells and group 3 innate lymphoid cells (ILC3) were more enriched in adult-onset severe asthma, whereas signatures associated with induced lung injury were less enriched in adult-onset severe asthma. Conclusions Adult-onset severe asthma is characterized by inflammatory pathways involving eosinophils, mast cells and ILC3s. These pathways could represent useful targets for the treatment of adult-onset severe asthma.
Publication Date: 26-Jul-2017
Date of Acceptance: 21-Jun-2017
URI: http://hdl.handle.net/10044/1/49601
DOI: https://dx.doi.org/10.1016/j.jaci.2017.06.037
ISSN: 1097-6825
Publisher: Elsevier
Start Page: 1280
End Page: 1290
Journal / Book Title: Journal of Allergy and Clinical Immunology
Volume: 141
Issue: 4
Copyright Statement: © 2017 Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/
Sponsor/Funder: Medical Research Council (MRC)
Medical Research Council (MRC)
Funder's Grant Number: G1000758
G1000758
Keywords: Adult-onset asthma
ILC3
eosinophils
gene set variation analysis
mast cells
mechanisms
phenotyping
severe asthma
transcriptomics
U-BIOPRED Study Group
1107 Immunology
Allergy
Publication Status: Published
Embargo Date: 2018-07-26
Appears in Collections:Faculty of Engineering
Computing
National Heart and Lung Institute
Airway Disease
Faculty of Medicine



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