Genetic profiles of transcriptomic clusters of childhood asthma determine specific severe subtype
Journal
Clinical and Experimental Allergy
Journal Volume
48
Journal Issue
9
Pages
1164-1172
Date Issued
2018
Author(s)
Abstract
Background: Previous studies have defined transcriptomic subtypes of adult asthma using samples of induced sputum and bronchial epithelium; however, those procedures are not readily applicable in the clinic, especially for childhood asthma. Objective: We aim to dissect the transcriptomic clusters of childhood asthma using highly variably expressed genes of peripheral blood mononuclear cells (PBMC) among patients. Methods: Gene expression of PBMC from 133 asthmatic children and 11 healthy controls was measured with Illumina microarrays. We applied the k-means clustering algorithm of 2048 genes to assign asthmatic children into clusters. Genes with differential expression between asthma clusters and healthy controls were used to investigate whether they could identify severe asthma of children and adults. Results: We identified 3 asthma clusters with distinct inflammatory profiles in peripheral blood. Cluster 1 had the highest eosinophil count. Cluster 2 showed lower counts of both eosinophils and neutrophils. Cluster 3 had the highest neutrophil count and the poorest treatment control. Compared with other patients, Cluster 3 exhibited a unique gene expression pattern which was associated with changes in the glucocorticoid signalling and activation of the T helper 1/T helper 17 (TH1/TH17) immune pathways. In the validation studies, an 84-gene signature could identify severe asthma in children on leucocytes, as well as severe asthma in adults on CD8+ T cells. Conclusions and Clinical Relevance: Gene expression profiling of PBMC is useful for the identification of TH1/TH17-mediated asthma with poor treatment control. PBMC and CD8+ T cells could be important targets for the investigation and identification of severe asthma. ? 2018 John Wiley & Sons Ltd
SDGs
Other Subjects
Article; asthma; CD4+ T lymphocyte; CD8+ T lymphocyte; child; controlled study; disease severity; eosinophil count; female; gene expression; gene expression profiling; human; leukocyte; major clinical study; male; neutrophil count; peripheral blood mononuclear cell; practice guideline; priority journal; school child; Taiwanese; Th1 cell; Th17 cell; transcriptomics; adolescent; age; asthma; biology; case control study; genetics; immunology; metabolism; mononuclear cell; preschool child; procedures; severity of illness index; signal transduction; T lymphocyte subpopulation; Taiwan; biological marker; reactive oxygen metabolite; transcriptome; Adolescent; Age Factors; Asthma; Biomarkers; Case-Control Studies; CD8-Positive T-Lymphocytes; Child; Child, Preschool; Computational Biology; Female; Gene Expression Profiling; Humans; Leukocytes, Mononuclear; Male; Reactive Oxygen Species; Severity of Illness Index; Signal Transduction; T-Lymphocyte Subsets; Taiwan; Th1 Cells; Th17 Cells; Transcriptome
Publisher
Blackwell Publishing Ltd
Type
journal article