IDENTIFYING KEY REGULATORY GENES IN THE WHOLE BLOOD OF SEPTIC PATIENTS TO MONITOR UNDERLYING IMMUNE DYSFUNCTIONS
IDENTIFYING KEY REGULATORY GENES IN THE WHOLE BLOOD OF SEPTIC PATIENTS TO MONITOR UNDERLYING IMMUNE DYSFUNCTIONS
复制标题
DOI：
10.1097/shk.0b013e31829ee604
复制
发表时间：
2013-09-01
期刊：
影响因子：
3.1
通讯作者：
McLean, Anthony S.
中科院分区：
文献类型：
--
作者：
Parnell, Grant P.;Tang, Benjamin M.;McLean, Anthony S.
目前没有可靠的工具可用于测量脓毒症患者在临床环境中的免疫功能障碍。这项概念验证研究评估了全血基因表达谱作为监测重症脓毒症患者免疫功能障碍的工具的潜力。每天从入住重症监护室的脓毒症患者中采集全血样本，持续长达5天。在由48，804个探针组成的Illumina HT-12基因表达微阵列上测定从全血样品分离的RNA。微阵列分析确定了3，677个基因在脓毒症患者和健康对照之间的5天内差异表达。在3，677个基因中，生物学途径分析鉴定出86个在脓毒症患者中显著下调的基因存在于与免疫应答相关的途径中。这86个基因对应于脓毒症中涉及的已知免疫途径，包括淋巴细胞耗竭、T淋巴细胞活化减少和抗原呈递缺陷。此外，这些基因的表达水平与临床严重程度相关，与幸存者相比，在非幸存者中发现了更大程度的下调。结果表明，全血基因表达分析可以捕获脓毒症患者的全身免疫功能障碍。我们的研究提供了一个实验基础，以支持进一步研究使用的基因表达为基础的检测，以评估免疫抑制，并在未来的临床试验中指导免疫治疗。
There is currently no reliable tool available to measure immune dysfunction in septic patients in the clinical setting. This proof-of-concept study assesses the potential of gene expression profiling of whole blood as a tool to monitor immune dysfunction in critically ill septic patients. Whole-blood samples were collected daily for up to 5 days from patients admitted to the intensive care unit with sepsis. RNA isolated from whole-blood samples was assayed on Illumina HT-12 gene expression microarrays consisting of 48,804 probes. Microarray analysis identified 3,677 genes as differentially expressed across 5 days between septic patients and healthy controls. Of the 3,677 genes, biological pathway analysis identified 86 genes significantly downregulated in the sepsis patients were present in pathways relating to immune response. These 86 genes correspond to known immune pathways implicated in sepsis, including lymphocyte depletion, reduced T-lymphocyte activation, and deficient antigen presentation. Furthermore, expression levels of these genes correlated with clinical severity, with a significantly greater degree of downregulation found in nonsurvivors compared with survivors. The results show that whole-blood gene expression analysis can capture systemic immune dysfunctions in septic patients. Our study provides an experimental basis to support further study on the use of a gene expression-based assay, to assess immunosuppression, and to guide immunotherapy in future clinical trials.