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

被引:76
作者
Wong, Hector R. [1 ,2 ,3 ]
Cvijanovich, Natalie Z. [4 ]
Hall, Mark [5 ]
Allen, Geoffrey L. [6 ]
Thomas, Neal J. [7 ]
Freishtat, Robert J. [8 ]
Anas, Nick [9 ]
Meyer, Keith [10 ]
Checchia, Paul A. [11 ]
Lin, Richard [12 ]
Bigham, Michael T. [13 ]
Sen, Anita [14 ]
Nowak, Jeffrey [15 ]
Quasney, Michael [16 ]
Henricksen, Jared W. [17 ]
Chopra, Arun [18 ]
Banschbach, Sharon [1 ,2 ]
Beckman, Eileen [1 ,2 ]
Harmon, Kelli [1 ,2 ]
Lahni, Patrick [1 ,2 ]
Shanley, Thomas P. [19 ]
机构
[1] Cincinnati Childrens Hosp Med Ctr, Div Crit Care Med, Cincinnati, OH 45223 USA
[2] Cincinnati Childrens Res Fdn, Cincinnati, OH 45223 USA
[3] Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati, OH 45267 USA
[4] Childrens Hosp & Res Ctr Oakland, Div Crit Care Med, Oakland, CA 94609 USA
[5] Nationwide Childrens Hosp, Div Crit Care Med, Columbus, OH 43205 USA
[6] Childrens Mercy Hosp, Div Crit Care Med, Kansas City, MO 64108 USA
[7] Penn State Hershey Childrens Hosp, Div Crit Care Med, Hershey, PA 17033 USA
[8] Childrens Natl Med Ctr, Div Emergency Med, Washington, DC 20010 USA
[9] Childrens Hosp Orange Cty, Div Crit Care Med, Orange, CA 92868 USA
[10] Miami Childrens Hosp, Div Crit Care Med, Miami, FL 33155 USA
[11] Texas Childrens Hosp, Div Crit Care Med, Houston, TX 77030 USA
[12] Childrens Hosp Philadelphia, Div Crit Care Med, Philadelphia, PA 19104 USA
[13] Akron Childrens Hosp, Div Crit Care Med, Akron, OH 44308 USA
[14] Columbia Univ, Morgan Stanley Childrens Hosp, Med Ctr, Div Crit Care Med, New York, NY 10032 USA
[15] Childrens Hosp & Clin Minnesota, Div Crit Care Med, Minneapolis, MN 55404 USA
[16] Childrens Hosp Wisconsin, Div Crit Care Med, Milwaukee, WI 53201 USA
[17] Primary Childrens Med Ctr, Div Crit Care Med, Salt Lake City, UT 84113 USA
[18] St Christophers Hosp Children, Div Crit Care Med, Philadelphia, PA 19134 USA
[19] Univ Michigan, CS Mott Childrens Hosp, Div Crit Care Med, Ann Arbor, MI 48103 USA
来源
CRITICAL CARE | 2012年 / 16卷 / 05期
基金
美国国家卫生研究院;
关键词
SEPTIC SHOCK; EXPRESSION PROFILES; SEPSIS; IDENTIFICATION; VALIDATION; IL-27;
D O I
10.1186/cc11847
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
Introduction: 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. Methods: 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. Results: 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. Conclusions: 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.
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页数:8
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