Leukocyte subset-derived genomewide expression profiles in pediatric septic shock

Hector R. Wong, Robert J. Freishtat, Marie Monaco, Kelli Odoms, Thomas P. Shanley

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

Objective: To directly assess whether genomewide expression profiles derived from leukocyte subsets are comparable to that of whole blood as measured by enrichment for genes corresponding to metabolic and signaling pathways. Design: Prospective observational study involving microarray-based bioinformatics based on RNA individually derived from whole blood, neutrophils, monocytes, and lymphocytes, respectively. Setting: Three pediatric intensive care units in the United States. Patients: Children <10 yrs of age: five normal control subjects and 13 meeting criteria for septic shock on day 1 of presentation to the pediatric intensive care unit. Interventions: None other than standard care. Measurements and Main Results: Baseline analyses using whole blood-derived RNA demonstrated increased expression of genes corresponding to signaling pathways involving innate immunity, redox balance, and protein ubiquitination and decreased expression of genes corresponding to the adaptive immune system. Subsequent analyses using leukocyte-specific RNA were congruent with the gene expression profiles demonstrated using whole blood-derived RNA as measured by enrichment for genes corresponding to metabolic and signaling pathways. Gene network analysis, derived from a composite gene list involving the individual gene expression profiles of neutrophils, monocytes, and lymphocytes, respectively, revealed a gene network corresponding to antigen presentation, cell-mediated immunity, and humoral-mediated immunity. Finally, a subanalysis focused on network gene nodes localized to the nuclear compartment revealed functional annotations related to transcriptional repression and epigenetic regulation. Conclusions: These data demonstrate that genome-level repression of adaptive immunity gene programs early in the course of pediatric septic shock remained evident when analyses were conducted using leukocyte subset-specific RNA.

Original languageEnglish (US)
Pages (from-to)349-355
Number of pages7
JournalPediatric Critical Care Medicine
Volume11
Issue number3
DOIs
StatePublished - May 2010

Keywords

  • T cell
  • antigen presentation
  • children
  • inflammation
  • microarray

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Critical Care and Intensive Care Medicine

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