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

Chih-Hsi Scott Kuo, Stelios Pavlidis, Matthew Loza, Fred Baribaud, Anthony Rowe, Iaonnis Pandis, Ana Sousa, Julie Corfield, Ratko Djukanovic, Rene Lutter, Peter J. Sterk, Charles Auffray, Yike Guo, Ian M. Adcock, Kian Fan Chung

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285 Citations (Scopus)

Abstract

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
Original languageEnglish
Article number1602135
JournalEuropean respiratory journal
Volume49
Issue number2
DOIs
Publication statusPublished - 2017

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