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Upper Airway Cell Transcriptomics Identify a Major New Immunological Phenotype with Strong Clinical Correlates in Young Children with Acute Wheezing.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2019 Mar 15; Vol. 202 (6), pp. 1845-1858. Date of Electronic Publication: 2019 Feb 11. - Publication Year :
- 2019
-
Abstract
- Asthma exacerbations are triggered by rhinovirus infections. We employed a systems biology approach to delineate upper-airway gene network patterns underlying asthma exacerbation phenotypes in children. Cluster analysis unveiled distinct IRF7 <superscript>hi</superscript> versus IRF7 <superscript>lo</superscript> molecular phenotypes, the former exhibiting robust upregulation of Th1/type I IFN responses and the latter an alternative signature marked by upregulation of cytokine and growth factor signaling and downregulation of IFN-γ. The two phenotypes also produced distinct clinical phenotypes. For IRF7 <superscript>lo</superscript> children, symptom duration prior to hospital presentation was more than twice as long from initial symptoms ( p = 0.011) and nearly three times as long for cough ( p < 0.001), the odds ratio of admission to hospital was increased more than 4-fold ( p = 0.018), and time to recurrence was shorter ( p = 0.015). In summary, our findings demonstrate that asthma exacerbations in children can be divided into IRF7 <superscript>hi</superscript> versus IRF7 <superscript>lo</superscript> phenotypes with associated differences in clinical phenotypes.<br /> (Copyright © 2019 by The American Association of Immunologists, Inc.)
- Subjects :
- Adolescent
Asthma immunology
Case-Control Studies
Child
Child, Preschool
Cluster Analysis
Female
Gene Regulatory Networks
Humans
Infant
Infant, Newborn
Male
Phenotype
Respiratory Sounds immunology
Transcriptome
Asthma genetics
Interferon Regulatory Factor-7 genetics
Respiratory Sounds genetics
Respiratory Tract Infections complications
Respiratory Tract Infections genetics
Respiratory Tract Infections immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 202
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 30745463
- Full Text :
- https://doi.org/10.4049/jimmunol.1800178