Pathway discovery using transcriptomic profiles in adult-onset severe asthma

Hekking, Pieter-Paul and Loza, Matt J. and Pavlidis, Stelios and de Meulder, Bertrand and Lefaudeux, Diane and Baribaud, Fred and Auffray, Charles and Wagener, Ariane H. and Brinkman, Paul and Lutter, Rene and Bansal, Aruna T. and Sousa, Ana R. and Bates, Steve A. and Pandis, Yannis and Fleming, Louise J. and Shaw, Dominique E. and Fowler, Stephen J. and Guo, Y. and Meiser, Andrea and Sun, Kai and Corfield, Julie and Howarth, Peter H. and Bel, Elisabeth H. and Adcock, Ian M. and Chung, Kian Fan and Djukanovic, Ratko and Sterk, Peter J. (2018) Pathway discovery using transcriptomic profiles in adult-onset severe asthma. Journal of Allergy and Clinical Immunology, 141 (4). pp. 1280-1290. ISSN 0091-6749

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Abstract

Background: Adult-onset severe asthma is characterized by highly symptomatic disease despite high-intensity asthma treatments. Understanding of the underlying pathways of this heterogeneous disease is needed for the development of targeted treatments. Gene set variation analysis is a statistical technique used to identify gene profiles in heterogeneous samples.

Objective: We sought 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 age >18 years) as compared with childhood-onset severe asthma (<18 years) were selected from the U-BIOPRED cohort. Gene expression was assessed on the total RNA of induced sputum (n 5 83), nasal brushings (n 5 41), and endobronchial brushings (n 5 65) and biopsies (n 5 47) (Affymetrix HT HG-U1331 PM). Gene set variation analysis was used to identify differentially enriched predefined gene signatures of leukocyte lineage, inflammatory and induced lung injury pathways.

Results: Significant differentially enriched gene signatures in patients with adult-onset as compared with 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 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 group 3 innate lymphoid cells. These pathways could represent useful targets for the treatment of adult-onset severe asthma.

Item Type: Article
Keywords: Adult-onset asthma, severe asthma, gene set variation analysis, phenotyping, transcriptomics, mechanisms, eosinophils, mast cells, ILC3
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Medicine > Division of Respiratory Medicine
Identification Number: https://doi.org/10.1016/j.jaci.2017.06.037
Depositing User: Eprints, Support
Date Deposited: 17 May 2018 09:53
Last Modified: 17 May 2018 16:39
URI: http://eprints.nottingham.ac.uk/id/eprint/51853

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