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T-helper cell type 2 (Th2) and non-Th2 molecular phenotypes of asthma using sputum transcriptomics in U-BIOPRED.

T-helper cell type 2 (Th2) and non-Th2 molecular phenotypes of asthma using sputum transcriptomics in U-BIOPRED.
T-helper cell type 2 (Th2) and non-Th2 molecular phenotypes of asthma using sputum transcriptomics in U-BIOPRED.
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.
0903-1936
Kuo, Chih-Hsi
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Pavlidis, Stelios
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Loza, Matthew
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Baribaud, Fred
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Rowe, Anthony
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Pandis, Ioannis
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Sousa, Ana
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Corfield, Julie
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Djukanovic, Ratko
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Lutter, Rene
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Sterk, Peter J.
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Auffrey, Charles
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Guo, Yike
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Adcock, Ian M.
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Chung, Kian Fan
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Kuo, Chih-Hsi
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Pavlidis, Stelios
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Loza, Matthew
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Baribaud, Fred
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Rowe, Anthony
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Pandis, Ioannis
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Sousa, Ana
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Corfield, Julie
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Djukanovic, Ratko
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Lutter, Rene
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Sterk, Peter J.
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Auffrey, Charles
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Guo, Yike
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Adcock, Ian M.
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Chung, Kian Fan
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Kuo, Chih-Hsi, Pavlidis, Stelios, Loza, Matthew, Baribaud, Fred, Rowe, Anthony, Pandis, Ioannis, Sousa, Ana, Corfield, Julie, Djukanovic, Ratko, Lutter, Rene, Sterk, Peter J., Auffrey, Charles, Guo, Yike, Adcock, Ian M. and Chung, Kian Fan (2017) T-helper cell type 2 (Th2) and non-Th2 molecular phenotypes of asthma using sputum transcriptomics in U-BIOPRED. European Respiratory Journal, 49 (2). (doi:10.1183/13993003.02135-2016). (PMID:28179442)

Record type: Article

Abstract

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.

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Accepted/In Press date: 3 November 2016
e-pub ahead of print date: 8 February 2017
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 405812
URI: https://eprints.soton.ac.uk/id/eprint/405812
ISSN: 0903-1936
PURE UUID: 91117e53-4bd5-4742-b803-1d1b9da9f683
ORCID for Ratko Djukanovic: ORCID iD orcid.org/0000-0001-6039-5612

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Date deposited: 18 Feb 2017 00:20
Last modified: 10 Dec 2019 01:58

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Contributors

Author: Chih-Hsi Kuo
Author: Stelios Pavlidis
Author: Matthew Loza
Author: Fred Baribaud
Author: Anthony Rowe
Author: Ioannis Pandis
Author: Ana Sousa
Author: Julie Corfield
Author: Rene Lutter
Author: Peter J. Sterk
Author: Charles Auffrey
Author: Yike Guo
Author: Ian M. Adcock
Author: Kian Fan Chung

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