Interleukin-27 is a novel candidate diagnostic biomarker for bacterial infection in critically ill children.

Interleukin-27 is a novel candidate diagnostic biomarker for bacterial infection in critically ill children.
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DOI:
10.1186/cc11847
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发表时间:
2012-10-29
期刊:
Critical care (London, England)
影响因子:
--
通讯作者:
Shanley TP
Shanley TP
中科院分区:
其他
文献类型:
--
作者:
Wong HR;Cvijanovich NZ;Hall M;Allen GL;Thomas NJ;Freishtat RJ;Anas N;Meyer K;Checchia PA;Lin R;Bigham MT;Sen A;Nowak J;Quasney M;Henricksen JW;Chopra A;Banschbach S;Beckman E;Harmon K;Lahni P;Shanley TP

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在有发热和其他全身炎症反应综合征(SIRS)迹象的危重患者中区分无菌炎症和细菌感染仍然是一个临床挑战。我们研究的目的是挖掘现有的全基因组表达数据库,以发现候选的诊断生物标记物,以预测危重儿童中细菌感染的存在。比较了细菌培养阴性的SIRS患者(n=21)和细菌培养阳性的脓毒症患者(n=60)的全基因组表达数据。差异表达的基因接受留一法交叉验证(LOOCV)以预测SIRS或脓毒症级别。对101例全身炎症反应综合征(SIRS)患者和130例脓毒症患者的血清白介素27(IL-27)和降钙素原(PCT)水平进行了比较。所有数据代表达到全身炎症反应综合征或脓毒症标准的前24小时。在SIRS患者和脓毒症患者之间,有221个基因探针被差异调控。LOOCV程序正确预测了86%的SIRS和脓毒症级别,而EB病毒诱导基因3(EBI3)的预测强度最高。基因表达嵌合体的计算机辅助图像分析能够预测感染的特异度为90%,阳性预测值为94%。由于EBI3是异源二聚体细胞因子IL-27的一个亚单位,我们测试了血清IL-27蛋白浓度预测感染的能力。以≥5 ng/ml为临界值,血清IL-27蛋白浓度预测感染的特异度和阳性预测值为90%,且IL-27的总体表现优于PCT。与单独使用任何一个生物标记物相比,结合IL-27和PCT的决策树改善了总体预测能力。全基因组表达分析为确定IL-27作为预测危重儿童细菌感染的新的候选诊断生物标志物提供了基础。还需要更多的研究来进一步测试IL-27的诊断性能。本文中报道的微阵列数据已登记在基因表达总览中,登录号为GSE4607。
Differentiating between sterile inflammation and bacterial infection in critically ill patients with fever and other signs of the systemic inflammatory response syndrome (SIRS) remains a clinical challenge. The objective of our study was to mine an existing genome-wide expression database for the discovery of candidate diagnostic biomarkers to predict the presence of bacterial infection in critically ill children. Genome-wide expression data were compared between patients with SIRS having negative bacterial cultures (n = 21) and patients with sepsis having positive bacterial cultures (n = 60). Differentially expressed genes were subjected to a leave-one-out cross-validation (LOOCV) procedure to predict SIRS or sepsis classes. Serum concentrations of interleukin-27 (IL-27) and procalcitonin (PCT) were compared between 101 patients with SIRS and 130 patients with sepsis. All data represent the first 24 hours of meeting criteria for either SIRS or sepsis. Two hundred twenty one gene probes were differentially regulated between patients with SIRS and patients with sepsis. The LOOCV procedure correctly predicted 86% of the SIRS and sepsis classes, and Epstein-Barr virus-induced gene 3 (EBI3) had the highest predictive strength. Computer-assisted image analyses of gene-expression mosaics were able to predict infection with a specificity of 90% and a positive predictive value of 94%. Because EBI3 is a subunit of the heterodimeric cytokine, IL-27, we tested the ability of serum IL-27 protein concentrations to predict infection. At a cut-point value of ≥5 ng/ml, serum IL-27 protein concentrations predicted infection with a specificity and a positive predictive value of >90%, and the overall performance of IL-27 was generally better than that of PCT. A decision tree combining IL-27 and PCT improved overall predictive capacity compared with that of either biomarker alone. Genome-wide expression analysis has provided the foundation for the identification of IL-27 as a novel candidate diagnostic biomarker for predicting bacterial infection in critically ill children. Additional studies will be required to test further the diagnostic performance of IL-27. The microarray data reported in this article have been deposited in the Gene Expression Omnibus under accession number GSE4607.
通过中和白细胞介素的生物学功能27来保护致死性败血性腹膜炎。
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