Upper Airway Cell Transcriptomics Identify a Major New Immunological Phenotype with Strong Clinical Correlates in Young Children with Acute Wheezing
| Autor: | Ingrid A. Laing, Siew-Kim Khoo, Stephen Oo, Franciska Prastanti, Peter N. Le Souëf, Laura Coleman, Niamh M. Troy, Janet Everard, Kimberley Franks, Lisa Öberg, Meredith L Borland, Anthony Bosco, James F. Read, Christopher McCrae, Joelene Bizzintino, Guicheng Zhang, Rose A. Maciewicz |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Adolescent Interferon Regulatory Factor-7 medicine.medical_treatment Immunology medicine.disease_cause Transcriptome Downregulation and upregulation Cluster Analysis Humans Immunology and Allergy Medicine Gene Regulatory Networks Child Respiratory Tract Infections Respiratory Sounds business.industry Infant Newborn Case-control study Infant Odds ratio Phenotype Asthma Cytokine Case-Control Studies Child Preschool Female Rhinovirus Airway business |
| Zdroj: | The Journal of Immunology. 202:1845-1858 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | 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 IRF7hi versus IRF7lo 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 IRF7lo 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 IRF7hi versus IRF7lo phenotypes with associated differences in clinical phenotypes. |
| Databáze: | OpenAIRE |
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