title: The influence of developmental age on the early transcriptomic response of children with septic shock.
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 school-age (≥ 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.
authors: Department of Pediatrics, Duke University School of Medicine, Durham, North Carolina, United States of America.
authors: James L
authors: JL
authors: Wynn
authors: Natalie Z
authors: NZ
authors: Cvijanovich
authors: Geoffrey L
authors: GL
authors: Allen
authors: Neal J
authors: NJ
authors: Thomas
authors: Robert J
authors: RJ
authors: Freishtat
authors: Nick
authors: N
authors: Anas
authors: Keith
authors: K
authors: Meyer
authors: Paul A
authors: PA
authors: Checchia
authors: Richard
authors: R
authors: Lin
authors: Thomas P
authors: TP
authors: Shanley
authors: Michael T
authors: MT
authors: Bigham
authors: Sharon
authors: S
authors: Banschbach
authors: Eileen
authors: E
authors: Beckman
authors: Hector R
authors: HR
authors: Wong
mesh_terms: D000375:Aging / Q000235:genetics*; D017951:Antigen Presentation / Q000235:genetics; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003710:Demography; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007249:Inflammation / Q000150:complications / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D012772:Shock, Septic / Q000150:complications / Q000235:genetics* / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics; D059467:Transcriptome / Q000235:genetics*
chemical_list: D016753:Interleukin-10