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


METHODS
Prospective observational study involving microarray-based bioinformatics based on RNA individually derived from whole blood, neutrophils, monocytes, and lymphocytes, respectively.


METHODS
Three pediatric intensive care units in the United States.


METHODS
Children < 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.


METHODS
None other than standard care.


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.
Wong
Hector R
HR
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
Freishtat
Robert J
RJ
Monaco
Marie
M
Odoms
Kelli
K
Shanley
Thomas P
TP
D002648:Child; D002675:Child, Preschool; D005260:Female; D020869:Gene Expression Profiling; D055106:Genome-Wide Association Study; D006801:Humans; D007223:Infant; D015278:Intensive Care Units, Pediatric; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D019370:Observation; D020411:Oligonucleotide Array Sequence Analysis; D011446:Prospective Studies; D012772:Shock, Septic / Q000097:blood*; D015398:Signal Transduction / Q000235:genetics; D014481:United States