RT Journal Article
SR Electronic
T1 T-helper cell type 2 (Th2) and non-Th2 molecular phenotypes of asthma using sputum transcriptomics in U-BIOPRED
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 1602135
DO 10.1183/13993003.02135-2016
VO 49
IS 2
A1 Chih-Hsi Scott Kuo
A1 Stelios Pavlidis
A1 Matthew Loza
A1 Fred Baribaud
A1 Anthony Rowe
A1 Iaonnis Pandis
A1 Ana Sousa
A1 Julie Corfield
A1 Ratko Djukanovic
A1 Rene Lutter
A1 Peter J. Sterk
A1 Charles Auffray
A1 Yike Guo
A1 Ian M. Adcock
A1 Kian Fan Chung
YR 2017
UL http://erj.ersjournals.com/content/49/2/1602135.abstract
AB Asthma is characterised by heterogeneous clinical phenotypes. Our objective was to determine molecular phenotypes of asthma by analysing sputum cell transcriptomics from 104 moderate-to-severe asthmatic subjects and 16 nonasthmatic subjects.After filtering on the differentially expressed genes between eosinophil- and noneosinophil-associated sputum inflammation, we used unbiased hierarchical clustering on 508 differentially expressed genes and gene set variation analysis of specific gene sets.We defined three transcriptome-associated clusters (TACs): TAC1 (characterised by immune receptors IL33R, CCR3 and TSLPR), TAC2 (characterised by interferon-, tumour necrosis factor-α- and inflammasome-associated genes) and TAC3 (characterised by genes of metabolic pathways, ubiquitination and mitochondrial function). TAC1 showed the highest enrichment of gene signatures for interleukin-13/T-helper cell type 2 (Th2) and innate lymphoid cell type 2. TAC1 had the highest sputum eosinophilia and exhaled nitric oxide fraction, and was restricted to severe asthma with oral corticosteroid dependency, frequent exacerbations and severe airflow obstruction. TAC2 showed the highest sputum neutrophilia, serum C-reactive protein levels and prevalence of eczema. TAC3 had normal to moderately high sputum eosinophils and better preserved forced expiratory volume in 1 s. Gene–protein coexpression networks from TAC1 and TAC2 extended this molecular classification.We defined one Th2-high eosinophilic phenotype TAC1, and two non-Th2 phenotypes TAC2 and TAC3, characterised by inflammasome-associated and metabolic/mitochondrial pathways, respectively.Clustering of transcriptomic genes from sputum cells defined one Th2- and two non-Th2-associated phenotypes http://ow.ly/UEkA3069ZYL