Pathway discovery using transcriptomic profiles in adult-onset severe asthma.

Hekking, Pieter-Paul; Loza, Matt J; Pavlidis, Stelios; de Meulder, Bertrand; Lefaudeux, Diane; Baribaud, Fred; Auffray, Charles; Wagener, Ariane H; Brinkman, Paul; Lutter, Rene; Bansal, Aruna T; Sousa, Ana R; Bates, Steve A; Pandis, Yannis; Fleming, Louise J; Shaw, Dominique E; Fowler, Stephen J; Guo, Y; Meiser, Andrea; Sun, Kai; ... (2018). Pathway discovery using transcriptomic profiles in adult-onset severe asthma. The Journal of allergy and clinical immunology, 141(4), pp. 1280-1290. Elsevier 10.1016/j.jaci.2017.06.037

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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 = 83), nasal brushings (n = 41), and endobronchial brushings (n = 65) and biopsies (n = 47) (Affymetrix HT HG-U133+ 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:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Pneumology 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Pneumologie (Erwachsene)
Subjects:	600 Technology > 610 Medicine & health
ISSN:	1097-6825
Publisher:	Elsevier
Language:	English
Submitter:	Rahel Holderegger
Date Deposited:	29 Nov 2017 09:47
Last Modified:	10 Apr 2018 01:30
Publisher DOI:	10.1016/j.jaci.2017.06.037
PubMed ID:	28756296
Additional Information:	Prof. Th. Geiser and Prof. Ch. von Garnier are members of the U-BIOPRED Research Group and Prof. Th. Geiser is mentioned as collaborator
Uncontrolled Keywords:	Adult-onset asthma ILC3 eosinophils gene set variation analysis mast cells mechanisms phenotyping severe asthma transcriptomics
URI:	https://boris.unibe.ch/id/eprint/107061