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 output: Contribution to journalArticlepeer-review

77 Scopus citations

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 schoolage (≥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.

Original languageEnglish (US)
Pages (from-to)1146-1156
Number of pages11
JournalMolecular Medicine
Volume17
Issue number11
DOIs
StatePublished - Nov 2011

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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