Perinatal granulopoiesis and risk of pediatric asthma
- University of Illinois at Chicago, United States
- Brigham and Women's Hospital, Harvard Medical School, United States
- University of Rochester, United States
- Harvard Medical School and Harvard Pilgrim Health Care Institute, United States
Abstract
There are perinatal characteristics, such as gestational age, reproducibly associated with risk for pediatric asthma. Identification of biologic processes influenced by these characteristics could facilitate risk stratification or new therapeutic targets. We hypothesized that transcriptional changes associated with multiple epidemiologic risk factors would be mediators of pediatric asthma risk. Using publicly available transcriptomic data from cord blood mononuclear cells, transcription of genes involved in myeloid differentiation were observed to be inversely associated with a pediatric asthma risk stratification based on multiple perinatal risk factors. This gene signature was validated in an independent prospective cohort and was specifically associated with genes localizing to neutrophil specific granules. Further validation demonstrated that umbilical cord blood serum concentration of PGLYRP-1, a specific granule protein, was inversely associated with mid-childhood current asthma and early-teen FEV1/FVCx100. Thus, neutrophil specific granule abundance at birth predicts risk for pediatric asthma and pulmonary function in adolescence.
Data availability
Data from RNAseq is available on NCBI Bioproject database PRJNA577955.
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Article and author information
Author details
Benjamin A Turturice
Funding
National Heart, Lung, and Blood Institute (F30HL136001)
- Benjamin A Turturice
National Institute of Allergy and Infectious Diseases (R01AI053878)
- Patricia W Finn
Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD034568)
- Emily Oken
National Institutes of Health (UH3OD023286)
- Emily Oken
Robert Wood Johnson Foundation (Nurse Faculty Scholars Program #72117)
- Mary Dawn Koenig
University of Illinois at Chicago (College of Nursing Dean's Award)
- Mary Dawn Koenig
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Mone Zaidi, Icahn School of Medicine at Mount Sinai, United States
Ethics
Human subjects: The current study was approved by the University of Illinois at Chicago IRB, 20160326 and 20150353, and the IRB of Harvard Pilgrim Health Care.
Version history
- Received: October 5, 2020
- Accepted: February 5, 2021
- Accepted Manuscript published: February 10, 2021 (version 1)
- Version of Record published: February 17, 2021 (version 2)
Copyright
© 2021, Turturice et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Perinatal granulopoiesis and risk of pediatric asthma
eLife 10:e63745.
https://doi.org/10.7554/eLife.63745
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