病毒性肺炎患者外周血干扰素刺激基因15 mRNA表达特征的研究

Study on the expressive characteristic of interferon stimulated gene 15 mRNA from peripheral blood of patients with viral pneumonia

通过分析病毒性肺炎患者外周血干扰素刺激基因15(interferon stimulated gene 15,ISG15)mRNA在感染状态下的特征性表达,探究ISG15与病毒性肺炎发病机制及疾病活动性之间的可能联系,为探索特异性呼吸道病毒感染的宿主生物标志物提供依据。本研究共收集157例社区获得性肺炎(community-acquired pneumonia,CAP)住院患者(CAP组)及40例健康人(健康对照组)的外周血样本和临床数据。157例CAP患者中呼吸道病毒感染患者133例,细菌性感染患者24例。采用实时反转录聚合酶链反应(real-time reverse transcription polymerase chain reaction,real-time RT-PCR)对不同病原体感染的CAP患者外周血ISG15 mRNA表达水平进行分析,同时通过体外病毒刺激外周血单个核细胞(peripheral blood mononuclear cell,PBMC)观察病毒载量与ISG15 mRNA之间的变化情况。结果显示ISG15 mRNA在部分呼吸道病毒感染组中表达水平显著增高,同健康对照组或细菌感染组相比均有显著差异;受试者操作特征(receiver operator characteristic,ROC)曲线分析显示,外周血ISG15 mRNA用于区分CAP组患者呼吸道病毒感染的ROC曲线下面积达73%(P=0.002);在全部入组的CAP患者组及健康对照组中用于诊断呼吸道病毒感染ROC曲线下面积达到77.5%(P=0.03)。体外分离的PBMC经病毒感染后,ISG15 mRNA表达基本与病毒RNA复制水平呈正相关变化。本研究证实外周血ISG15 mRNA高水平表达与呼吸道病毒感染密切相关,提示外周血ISG15 mRNA可能在病毒性肺炎的鉴别诊断中具有重要的临床价值。

This study analyzed the peripheral blood interferon stimulated gene 15(ISG15 mRNA)expression levels in viral pneumonia and bacterial pneumonia patients and discussed the possible relationship between ISG15 and the pathogenesis of viral pneumonia,providing further clinical evidences for host markers of specific respiratory virus infections.In this study,Peripheral blood samples were collected from 157 community acquired pneumonia(CAP)hospitalized patients and 40 healthy people(healthy controls)as well as their clinical data.The patients include 133 with viral respiratory tract infection and 24 patients with bacterial infection.The ISG15 mRNA expression levels for all samples were analyzed by real-time reverse transcription polymerase chain reaction(real-time RT-PCR).We validated the ISG15 mRNA expression by stimulating the peripheral blood mononuclear cell(PBMC)in vitro and analyzing the correlation between viral load and ISG15 mRNA levels.The expression level of ISG15 mRNA in the viral respiratory infection group was significantly higher than that in the healthy control group and the bacterial infection group.Receiver operating characteristic(ROC)curves analysis showed that the ISG15 mRNA in peripheral blood had a potential diagnostic value to distinguish viral respiratory infection and bacterial infection in adult CAP patients.In vitro studies also showed that there was a positive correlation between ISG15 mRNA expression in PBMC and viral replication.The peripheral blood ISG15 mRNA expression level was highly correlated with viral respiratory infection by analyzing the clinical data and in vitro experiments.This study demonstrated that ISG15 mRNA in peripheral blood may have an important clinical value in diagnosis of viral pneumonia.