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

Full text not available from this repository. (Request a copy)

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

Actions (login required)

Edit item Edit item
Provide Feedback