BibTex format
@article{Kuo:2017:10.1183/13993003.02135-2016,
author = {Kuo, C-HS and Pavlidis, S and Loza, M and Baribaud, F and Rowe, A and Pandis, I and Sousa, A and Corfield, J and Djukanovic, R and Lutter, R and Sterk, PJ and Auffray, C and Guo, Y and Adcock, IM and Chung, KF},
doi = {10.1183/13993003.02135-2016},
journal = {European Respiratory Journal},
title = {T-helper cell type 2 (Th2) and non-Th2 molecular phenotypes of asthma using sputum transcriptomics in U-BIOPRED},
url = {http://dx.doi.org/10.1183/13993003.02135-2016},
volume = {49},
year = {2017}
}
RIS format (EndNote, RefMan)
TY - JOUR
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 1s. 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.
AU - Kuo,C-HS
AU - Pavlidis,S
AU - Loza,M
AU - Baribaud,F
AU - Rowe,A
AU - Pandis,I
AU - Sousa,A
AU - Corfield,J
AU - Djukanovic,R
AU - Lutter,R
AU - Sterk,PJ
AU - Auffray,C
AU - Guo,Y
AU - Adcock,IM
AU - Chung,KF
DO - 10.1183/13993003.02135-2016
PY - 2017///
SN - 0903-1936
TI - T-helper cell type 2 (Th2) and non-Th2 molecular phenotypes of asthma using sputum transcriptomics in U-BIOPRED
T2 - European Respiratory Journal
UR - http://dx.doi.org/10.1183/13993003.02135-2016
UR - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000397858100033&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR - http://hdl.handle.net/10044/1/51554
VL - 49
ER -