The Influence of Developmental Age on the Early Transcriptomic Response of Children with Septic Shock
The Influence of Developmental Age on the Early Transcriptomic Response of Children with Septic Shock
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DOI：
10.2119/molmed.2011.00169
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发表时间：
2011-11-01
影响因子：
5.7
通讯作者：
Wong, Hector R.
中科院分区：
文献类型：
--
作者：
Wynn, James L.;Cvijanovich, Natalie Z.;Wong, Hector R.
感染性休克是儿科重症监护病房（PICU）患者中常见且费用高昂的问题，并且与高死亡率和毁灭性的幸存者发病率相关。全基因组表达模式可以提供宿主反应的分子粒度，并提供对结果存在较大差异的原因的深入了解。我们从感染性休克儿童入院后24小时内获得全血全基因组表达模式。我们比较了感染性休克发育年龄组（定义为新生儿（= 6岁，n = 47）和年龄匹配的对照组）之间的转录组。直接组间比较表明，新生儿的深刻变化，相对于年龄较大的儿童。感染性休克的新生儿表现出代表先天性和适应性免疫关键途径的基因表达减少。与所有其他组中转录组大幅上调相反，与对照组相比，新生儿表现出主要下调的转录组。新生儿和学龄期受试者相对于对照组具有最独特的调控基因。对宿主反应的特异性研究是必要的，以确定发育相关的翻译机会，可能会导致改善脓毒症的结果。(C)2011 Feinstein医学研究所，www.feinsteininstitute.org在线地址：http://www.molmed.org doi：10.2119/molmed.2011.00169
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 (= 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. (C) 2011 The Feinstein Institute for Medical Research, www.feinsteininstitute.org Online address: http://www.molmed.org doi: 10.2119/molmed.2011.00169