流式细胞术细胞因子谱检测在脓毒症诊断及死亡风险评估中的临床应用  

Clinical application of flow cytometric cytokine profiling in diagnosis of sepsis and assessment of mortality risk

作　　者：马晋 杨浩 孙昌瑞 雷雨 吴春香 Ma Jin;Yang Hao;Sun Changrui;Lei Yu;Wu Chunxiang(Department of Laboratory Medicine,Sichuan Academy of Medical Sciences&Sichuan Provincial People’s Hospital,Sichuan Academy of Medical Sciences&Sichuan Provincial People’s Hospital;Department of Medicine,Sichuan Academy of Medical Sciences&Sichuan Provincial People’s Hospital,Sichuan Academy of Medical Sciences&Sichuan Provincial People’s Hospital;Department of Critical Care Medicine,Sichuan Academy of Medical Sciences&Sichuan Provincial People’s Hospital)

机构地区：[1]四川省医学科学院/四川省人民医院临床医学检验中心,成都610072 [2]四川省医学科学院/四川省人民医院医务部,成都610072 [3]四川省医学科学院/四川省人民医院重症医学科,成都610072

出　　处：《重庆医科大学学报》2024年第12期1600-1607,共8页Journal of Chongqing Medical University

基　　金：四川省科技计划重点研发资助项目(编号:2022YFS0238)。

摘　　要：目的:研究流式细胞术细胞珠阵列(cytometric bead array,CBA)法检测脓毒症患者人细胞因子谱表达水平,探讨并比较各细胞因子在脓毒症患者早期诊断及预测死亡风险中的临床应用价值。方法:纳入256例ICU脓毒症患者,99例健康体检者和99例ICU非脓毒症患者,流式细胞术CBA法检测入组人群入院当天血浆IL-2、IL-4、IL-6、IL-10、TNF-α和IFN-γ的水平。Spearman及R语言Mantel检验分别用于常规相关性分析和指标集合间的相关性分析,构建受试者工作特征曲线(receiver operating characteristic,ROC)曲线,评估并比较人细胞因子谱中各细胞因子对脓毒症患者早期诊断及预估死亡风险的应用价值。结果:脓毒症患者血浆人细胞因子谱中IL-6、IL-10水平明显高于健康对照及ICU非脓毒症患者。IL-6的早期脓毒症诊断ROC曲线下面积(area under curve,AUC)为0.868(P<0.0001,95%CI=0.835~0.901),IL-10为0.831(P<0.0001,95%CI=0.793~0.869)。Mantel检验指标集合间的相关性分析显示:在脓毒症患者死亡组中,IL-6与CRP呈显著相关性(r=0.101,P=0.001),IL-10与NEUT呈显著相关性(r=0.132,P=0.001)。人细胞因子谱中的各细胞因子预测28 d死亡率的AUC均低于0.70。结论:使用流式细胞术CBA法检测人细胞因子在脓毒症早期诊断中表现出不同的效力。IL-6和IL-10能为脓毒症的早期临床诊断提供证据,但在预估死亡风险方面与其他因子效力相当。Objective:To investigate the cytometric bead array(CBA)method in measuring the expression levels of human cytokine profiles in patients with sepsis,and to explore the clinical application value of different cytokines in the early diagnosis of sepsis and the prediction of mortality risk.Methods:This study was conducted among 256 sepsis patients admitted to the intensive care unit(ICU),99 healthy individuals who underwent physical examination,and 99 non-sepsis patients admitted to the ICU,and the CBA method was used to measure the plasma levels of interleukin-2(IL-2),interleukin-4(IL-4),interleukin-6(IL-6),interleukin-10(IL-10),tumor necrosis factor-α(TNF-α),and interferon gamma(IFN-γ).The Spearman and Mantel tests in R language were used for the routine correlation analysis and the correlation analysis between indicator sets,and the receiver operating characteristic(ROC)curve was plotted to assess the application value of each cytokine in the human cytokine profile in the early diagnosis of sepsis patients and the prediction of mortality risk.Results:The sepsis patients had significantly higher plasma levels of IL-6 and IL-10 in the human cytokine profile than the healthy controls and the non-sepsis patients admitted to the ICU.IL-6 had an area under the ROC curve(AUC)of 0.868(95%CI=0.835-0.901,P<0.0001)in the early diagnosis of sepsis,while IL-10 had an AUC of 0.831(95%CI=0.793-0.869,P<0.0001).The correlation analysis of the indicator sets using the Mantel test showed a significant correlation between IL-6 and C-reactive protein in the sepsis mortality group(r=0.101,P=0.001),as well as a significant correlation between IL-10 and neutrophil count(r=0.132,P=0.001).All cytokines in the human cytokine profile had an AUC of<0.70 in predicting 28-day mortality rate.Conclusion:Human cytokines measured by the CBA method have varying degrees of efficacy in the early diagnosis of sepsis.While IL-6 and IL-10 can offer valuable evidence for the early clinical diagnosis of sepsis,they have comparable efficacy to other cyto

关 键 词：细胞因子谱 脓毒症预后 白介素-6 白介素-10 生物标志物 

分 类 号：R473.72[医药卫生—护理学]