A distinct influenza infection signature in the blood transcriptome of patients with severe community-acquired pneumonia
A distinct influenza infection signature in the blood transcriptome of patients with severe community-acquired pneumonia
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DOI：
10.1186/cc11477
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发表时间：
2012-01-01
期刊：
影响因子：
15.1
通讯作者：
Tang, Benjamin M.
中科院分区：
文献类型：
--
作者：
Parnell, Grant P.;McLean, Anthony S.;Tang, Benjamin M.
简介：由于流感病毒的存在与临床状态之间缺乏相关性，严重流感肺炎的诊断仍然具有挑战性。我们进行了基因表达谱在危重病人的全血中，以确定一个基因签名，使临床医生区分流感感染从其他原因的严重呼吸衰竭，如细菌性肺炎，和非感染性全身炎症反应syndrome.Methods：全血样本收集危重病人和Illumina HT-12基因表达beadarrays分析。结果：H1N1甲型流感肺炎与细菌性肺炎和全身炎症反应综合征的基因表达谱存在明显差异。流感基因表达谱的特征在于来自细胞周期调节、细胞凋亡和DNA损伤反应途径的基因的上调。相比之下，在细菌性肺炎或全身炎症反应综合征患者中没有发现独特的基因表达特征。流感感染的基因表达谱持续5天的随访。此外，在原发性H1N1甲型流感病毒感染的患者中，细菌合并感染随后发展，流感基因表达签名保持不变，尽管存在叠加的细菌infection.Conclusions：全血表达谱数据表明，宿主对流感肺炎的反应是明显不同的细菌病原体引起的。这些信息可以加快识别严重呼吸衰竭患者的感染原因，从而更快地进行适当的患者护理。
Introduction: Diagnosis of severe influenza pneumonia remains challenging because of a lack of correlation between the presence of influenza virus and clinical status. We conducted gene-expression profiling in the whole blood of critically ill patients to identify a gene signature that would allow clinicians to distinguish influenza infection from other causes of severe respiratory failure, such as bacterial pneumonia, and noninfective systemic inflammatory response syndrome.Methods: Whole-blood samples were collected from critically ill individuals and assayed on Illumina HT-12 gene-expression beadarrays. Differentially expressed genes were determined by linear mixed-model analysis and overrepresented biological pathways determined by using GeneGo MetaCore.Results: The gene-expression profile of H1N1 influenza A pneumonia was distinctly different from those of bacterial pneumonia and systemic inflammatory response syndrome. The influenza gene-expression profile is characterized by upregulation of genes from cell-cycle regulation, apoptosis, and DNA-damage-response pathways. In contrast, no distinctive gene-expression signature was found in patients with bacterial pneumonia or systemic inflammatory response syndrome. The gene-expression profile of influenza infection persisted through 5 days of follow-up. Furthermore, in patients with primary H1N1 influenza A infection in whom bacterial co-infection subsequently developed, the influenza gene-expression signature remained unaltered, despite the presence of a superimposed bacterial infection.Conclusions: The whole-blood expression-profiling data indicate that the host response to influenza pneumonia is distinctly different from that caused by bacterial pathogens. This information may speed the identification of the cause of infection in patients presenting with severe respiratory failure, allowing appropriate patient care to be undertaken more rapidly.