• Pediatr Crit Care Me · May 2010

    Leukocyte subset-derived genomewide expression profiles in pediatric septic shock.

    • Hector R Wong, Robert J Freishtat, Marie Monaco, Kelli Odoms, and Thomas P Shanley.
    • Cincinnati Children's Hospital Medical Center and Cincinnati Children's Research Foundation, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA. hector.wong@cchmc.org
    • Pediatr Crit Care Me. 2010 May 1;11(3):349-55.

    ObjectiveTo 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.DesignProspective observational study involving microarray-based bioinformatics based on RNA individually derived from whole blood, neutrophils, monocytes, and lymphocytes, respectively.SettingThree pediatric intensive care units in the United States.PatientsChildren < or =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.InterventionsNone other than standard care.Measurements And Main ResultsBaseline 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.ConclusionsThese 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.

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