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Molecular Medicine

, Volume 17, Issue 11–12, pp 1146–1156 | Cite as

The Influence of Developmental Age on the Early Transcriptomic Response of Children with Septic Shock

  • James L. Wynn
  • Natalie Z. Cvijanovich
  • Geoffrey L. Allen
  • Neal J. Thomas
  • Robert J. Freishtat
  • Nick Anas
  • Keith Meyer
  • Paul A. Checchia
  • Richard Lin
  • Thomas P. Shanley
  • Michael T. Bigham
  • Sharon Banschbach
  • Eileen Beckman
  • Hector R. Wong
Research Article

Abstract

Septic shock is a frequent and costly problem among patients in the pediatric intensive care unit (PICU) and is associated with high mortality and devastating survivor morbidity. Genome-wide expression patterns can provide molecular granularity of the host response and offer insight into why large variations in outcomes exist. We derived whole-blood genome-wide expression patterns within 24 h of PICU admission from children with septic shock. We compared the transcriptome between septic shock developmental-age groups defined as neonates (≤28 d, n = 17), infants (1 month to 1 year, n = 62), toddlers (2–5 years, n = 54) and school-age (≥6 years, n = 47) and age-matched controls. Direct intergroup comparisons demonstrated profound changes in neonates, relative to older children. Neonates with septic shock demonstrated reduced expression of genes representing key pathways of innate and adaptive immunity. In contrast to the largely upregulated transcriptome in all other groups, neonates exhibited a predominantly downregulated transcriptome when compared with controls. Neonates and school-age subjects had the most uniquely regulated genes relative to controls. Age-specific studies of the host response are necessary to identify developmentally relevant translational opportunities that may lead to improved sepsis outcomes.

Notes

Acknowledgments

This study was supported by grants from the National Institutes of Health (R01GM064619 and RC1HL100474).

The authors wish to thank Dr. Philip O. Scumpia for his careful review of the manuscript and comments.

Supplementary material

10020_2011_17111146_MOESM1_ESM.pdf (1.2 mb)
Supplementary material, approximately 1229 KB.

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Copyright information

© The Feinstein Institute for Medical Research 2011

Authors and Affiliations

  • James L. Wynn
    • 1
  • Natalie Z. Cvijanovich
    • 2
  • Geoffrey L. Allen
    • 3
  • Neal J. Thomas
    • 4
  • Robert J. Freishtat
    • 5
  • Nick Anas
    • 6
  • Keith Meyer
    • 7
  • Paul A. Checchia
    • 8
  • Richard Lin
    • 9
  • Thomas P. Shanley
    • 10
  • Michael T. Bigham
    • 11
  • Sharon Banschbach
    • 12
  • Eileen Beckman
    • 12
  • Hector R. Wong
    • 12
  1. 1.Department of PediatricsDuke University School of MedicineDurhamUSA
  2. 2.Children’s Hospital and Research Center OaklandOaklandUSA
  3. 3.Children’s Mercy HospitalKansas CityUSA
  4. 4.Penn State Children’s HospitalHersheyUSA
  5. 5.Children’s National Medical CenterWashington, DCUSA
  6. 6.Children’s Hospital of Orange CountyOrangeUSA
  7. 7.Miami Children’s HospitalMiamiUSA
  8. 8.St. Louis Children’s HospitalSt. LouisUSA
  9. 9.The Children’s Hospital of PhiladelphiaPhiladelphiaUSA
  10. 10.CS Mott Children’s Hospital at the University of MichiganAnn ArborUSA
  11. 11.Akron Children’s HospitalAkronUSA
  12. 12.Division of Critical Care Medicine-MLC 2005, Cincinnati Children’s Hospital Medical Center and Cincinnati Children’s Research Foundation, Department of PediatricsUniversity of Cincinnati College of MedicineCincinnatiUSA

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