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The influence of developmental age on the early transcriptomic response of children with septic shock

James L Wynn1, Natalie Z Cvijanovich, Geoffrey L Allen

  • 1Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina, United States of America.

Molecular Medicine (Cambridge, Mass.)
|July 9, 2011
PubMed

Insights

Septic shock impacts children differently by age. Neonates show reduced immune gene expression, unlike older children, highlighting the need for age-specific sepsis treatments.

Area of Science:

  • Pediatric critical care medicine
  • Immunology
  • Genomics

Background:

  • Septic shock is a significant cause of mortality and morbidity in pediatric intensive care units (PICUs).
  • Host response variations contribute to diverse patient outcomes.
  • Genome-wide expression patterns offer molecular insights into sepsis pathogenesis.

Purpose of the Study:

  • To investigate age-specific differences in the host's genomic response to septic shock in children.
  • To compare gene expression patterns across distinct developmental age groups admitted to the PICU with septic shock.

Main Methods:

  • Whole-blood genome-wide expression patterns were analyzed within 24 hours of PICU admission for children with septic shock.
  • Transcriptomes were compared between septic shock groups: neonates (≤28 days), infants (1 month-1 year), toddlers (2-5 years), and school-age children (≥6 years).
  • Age-matched controls were used for comparison.

Main Results:

  • Neonates with septic shock exhibited profound differences compared to older children.
  • Neonates showed reduced expression of genes in key innate and adaptive immunity pathways.
  • Unlike other age groups with upregulated transcriptomes, neonates displayed a predominantly downregulated transcriptome relative to controls.
  • Neonates and school-age children had the most uniquely regulated genes.

Conclusions:

  • Significant age-dependent variations exist in the host response to pediatric septic shock.
  • Neonatal sepsis involves distinct immune gene expression profiles compared to older children.
  • Age-specific research is crucial for developing targeted therapies to improve sepsis outcomes in children.

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