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Author Notes:

Jocelyn R. Grunwell, Email: jgrunwe@emory.edu

J.G., A.F., and R.K. conceived and developed the study, supervised the acquisition of the biological data, analyzed and interpreted the data. J.G. drafted and edited the manuscript. R.K. and A.F. assisted with drafting and editing the manuscript. M.R. helped with data analysis and edited the manuscript. S.S. and A.M. helped with patient sample processing, performed experiments and edited the manuscript. C.O. assisted in identifying, consenting, acquiring patient samples and assisted in collecting clinical information about the patients. All authors edited and approved the final version of this manuscript.

This study was supported in part by the Emory Integrated Genomics Core (EIGC), which is subsidized by the Emory University School of Medicine and is one of the Emory Integrated Core Facilities. Additional support was provided by the Georgia Clinical & Translational Science Alliance of the National Institutes of Health under Award Number UL1TR002378. The content is solely the responsibility of the authors and does not necessarily reflect the official views of the National Institutes of Health. The authors thank the bedside caregivers of the patients involved in this study for their skilled and compassionate care. Funding was provided by NIH Grants K23 HL151897 to JG. Funding was provided by the NIH Grant K24 NR018866 and R01 NR018666 to AF. Funding was provided by the NIH Grant Numbers R01 GM139967 and UL1 TR002378 to RK.

The authors declare no competing interests.

Subjects:

Research Funding:

Funding was provided by NIH Grants K23 HL151897 to JG. Funding was provided by the NIH Grant K24 NR018866 and R01 NR018666 to AF.

Funding was provided by the NIH Grant Numbers R01 GM139967 and UL1 TR002378 to RK.

Keywords:

  • Science & Technology
  • Multidisciplinary Sciences
  • Science & Technology - Other Topics
  • EXACERBATION-PRONE ASTHMA
  • LATENT CLASS ANALYSIS
  • NLRP3 INFLAMMASOME
  • PHENOTYPES
  • RNA

Functional immunophenotyping of children with critical status asthmaticus identifies differential gene expression responses in neutrophils exposed to a poly(I:C) stimulus

Journal Title:

SCIENTIFIC REPORTS

Volume:

Volume 12, Number 1

Publisher:

, Pages 19644-19644

Type of Work:

Article | Final Publisher PDF

Abstract:

The host immune response to a viral immune stimulus has not been examined in children during a life-threatening asthma attack. We determined whether we could identify clusters of children with critical asthma by functional immunophenotyping using an intracellular viral analog stimulus. We performed a single-center, prospective, observational cohort study of 43 children ages 6–17 years admitted to a pediatric intensive care unit for an asthma attack between July 2019 to February 2021. Neutrophils were isolated from children, stimulated overnight with LyoVec poly(I:C), and mRNA was analyzed using a targeted Nanostring immunology array. Network analysis of the differentially expressed transcripts for the paired LyoVec poly(I:C) samples was performed. We identified two clusters by functional immunophenotyping that differed by the Asthma Control Test score. Cluster 1 (n = 23) had a higher proportion of children with uncontrolled asthma in the four weeks prior to PICU admission compared with cluster 2 (n = 20). Pathways up-regulated in cluster 1 versus cluster 2 included chemokine receptor/chemokines, interleukin-10 (IL-10), IL-4, and IL-13 signaling. Larger validation studies and clinical phenotyping of children with critical asthma are needed to determine the predictive utility of these clusters in a larger clinical setting.

Copyright information:

© The Author(s) 2022

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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