Pathway discovery using transcriptomic profiles in adult-onset severe asthma

Publication date: Available online 26 July 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Pieter-Paul Hekking, Matt J. Loza, Stelios Pavlidis, Bertrand De Meulder, Diane Lefaudeux, Fred Baribaud, Charles Auffray, Ariane H. Wagener, Paul Brinkman, Rene. Lutter, ArunaT. Bansal, Ana R. Sousa, Steve. Bates, Yannis Pandis, Louise J. Fleming, Dominique E. Shaw, Stephen J. Fowler, Y. Guo, Andrea Meiser, Kai Sun, Julie. Corfield, Peter. Howarth, Elisabeth H. Bel, Ian M. Adcock, K.F. Chung, Ratko Djukanovic, Peter J. Sterk
RationaleAdult-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.ObjectiveTo identify gene profiles associated with adult-onset severe asthma.MethodsThis 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.ResultsSignificant 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.ConclusionsAdult-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.

Graphical abstract

Teaser

This study elucidates distinct gene profiles in adult-onset severe asthma compared to childhood-onset severe asthma. Identified gene profiles include those associated with eosinophils, ILC3s and mast cells, and may represent targets for new treatments.


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