Cincinnati Children's Hospital Medical Center and Cincinnati Children's Research Foundation, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Pediatr Crit Care Med. 2010 May;11(3):349-55. doi: 10.1097/PCC.0b013e3181c519b4.
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.
Prospective observational study involving microarray-based bioinformatics based on RNA individually derived from whole blood, neutrophils, monocytes, and lymphocytes, respectively.
Three pediatric intensive care units in the United States.
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.
None other than standard care.
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.
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.
直接评估通过富集代谢和信号通路相关基因，从白细胞亚群中获得的全基因组表达谱是否与全血相当。
前瞻性观察性研究，涉及基于微阵列的生物信息学，分别基于全血、中性粒细胞、单核细胞和淋巴细胞中各自分离的 RNA。
美国三个儿科重症监护病房。
<或=10 岁的儿童：5 名正常对照者和 13 名在入儿科重症监护病房的第 1 天符合败血症性休克标准的患者。
除标准治疗外无其他干预。
使用全血衍生的 RNA 进行的基线分析显示，涉及固有免疫、氧化还原平衡和蛋白质泛素化的信号通路相关基因表达增加，而适应免疫系统相关基因表达减少。随后使用白细胞特异性 RNA 进行的分析与使用全血衍生 RNA 进行的基因表达谱一致，如通过富集代谢和信号通路相关基因来衡量。源自涉及中性粒细胞、单核细胞和淋巴细胞各自的单个基因表达谱的复合基因列表的基因网络分析，揭示了一个与抗原呈递、细胞介导的免疫和体液介导的免疫相对应的基因网络。最后，一个侧重于网络基因节点定位于核区室的子分析揭示了与转录抑制和表观遗传调控相关的功能注释。
这些数据表明，在儿科败血症性休克发生的早期，适应性免疫基因程序的全基因组抑制在使用白细胞亚群特异性 RNA 进行分析时仍然明显。
