1. Immunology and Inflammation
  2. Medicine
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Perinatal granulopoiesis and risk of pediatric asthma

  1. Benjamin A Turturice  Is a corresponding author
  2. Juliana Theorell
  3. Mary Dawn Koenig
  4. Lisa Tussing-Humphreys
  5. Diane R Gold
  6. Augusto A Litonjua
  7. Emily Oken
  8. Sheryl L Rifas-Shiman
  9. David L Perkins  Is a corresponding author
  10. Patricia W Finn  Is a corresponding author
  1. University of Illinois at Chicago, United States
  2. Brigham and Women's Hospital, Harvard Medical School, United States
  3. University of Rochester, United States
  4. Harvard Medical School and Harvard Pilgrim Health Care Institute, United States
Research Article
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Cite this article as: eLife 2021;10:e63745 doi: 10.7554/eLife.63745

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.

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Benjamin A Turturice

    Department of Microbiology and Immunology, Department of Medicine, University of Illinois at Chicago, Chicago, United States
    For correspondence
    bturtu2@uic.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9382-4612
  2. Juliana Theorell

    Department of Medicine, University of Illinois at Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Mary Dawn Koenig

    Department of Women, Children and Family Health Science, University of Illinois at Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Lisa Tussing-Humphreys

    Department of Medicine and Cancer Center, University of Illinois at Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Diane R Gold

    Channing Division of Network Medicine, Department of Medicine, Department of Environmental Health, Harvard T.H. Chan School of Public Health, Brigham and Women's Hospital, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Augusto A Litonjua

    Department of Pediatrics, University of Rochester, Rochester, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Emily Oken

    Division of Chronic Disease Research Across the Life Course, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Sheryl L Rifas-Shiman

    Division of Chronic Disease Research Across the Life Course, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. David L Perkins

    Department of Medicine, University of Illinois at Chicago, Chicago, United States
    For correspondence
    perkinsd@uic.edu
    Competing interests
    The authors declare that no competing interests exist.
  10. Patricia W Finn

    Department of Microbiology and Immunology, Department of Medicine, Department of Bioengineering, University of Illinois at Chicago, Chicago, United States
    For correspondence
    pwfinn@uic.edu
    Competing interests
    The authors declare that no competing interests exist.

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.

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.

Reviewing Editor

  1. Mone Zaidi, Icahn School of Medicine at Mount Sinai, United States

Publication history

  1. Received: October 5, 2020
  2. Accepted: February 5, 2021
  3. Accepted Manuscript published: February 10, 2021 (version 1)
  4. 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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