Research
Interleukin-27 is a novel candidate diagnostic biomarker for bacterial infection in critically ill children
1 Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center and Cincinnati Children's Research Foundation, 3333 Burnet Ave, Cincinnati, OH 45223, USA
2 Department of Pediatrics, University of Cincinnati College of Medicine, 231 Albert Sabin Way, Cincinnati, OH 45267, USA
3 Division of Critical Care Medicine, Children's Hospital and Research Center Oakland, 744 52nd Street, Oakland, CA 64609, USA
4 Division of Critical Care Medicine, Nationwide Children's Hospital, 700 Children's Drive, Columbus, OH 43205, USA
5 Division of Critical Care Medicine, Children's Mercy Hospital, 2401 Gilham Road, Kansas City, MO 64108, USA
6 Division of Critical Care Medicine, Penn State Hershey Children's Hospital, 500 University Drive, Hershey, PA 17033, USA
7 Division of Emergency Medicine, Children's National Medical Center, 111 Michigan Avenue, Washington, DC 20010, USA
8 Division of Critical Care Medicine, Children's Hospital of Orange County, 455 South Main Street, Orange, CA 92868, USA
9 Division of Critical Care Medicine, 3100 SW 62nd Avenue, Miami Children's Hospital, Miami, FL 33155, USA
10 Division of Critical Care Medicine, 6621 Fannin Street, Texas Children's Hospital, Houston, TX 77030, USA
11 Division of Critical Care Medicine, The Children's Hospital of Philadelphia, 34th Street and Civic Center Boulevard, Philadelphia, PA 19104, USA
12 Division of Critical Care Medicine, Akron Children's Hospital, One Perkins Square, Akron, OH 44308, USA
13 Division of Critical Care Medicine, Morgan Stanley Children's Hospital, Columbia University Medical Center, 3959 Broadway, New York, NY 10032, USA
14 Division of Critical Care Medicine, Children's Hospital and Clinics of Minnesota, 2525 Chicago Avenue South, Minneapolis, MN 55404, USA
15 Division of Critical Care Medicine, Children's Hospital of Wisconsin, 9000 W Wisconsin Avenue, Milwaukee, WI 53201, USA
16 Division of Critical Care Medicine, Primary Children's Medical Center, 100 Mario Capecchi Drive, Salt Lake City, UT 84113, USA
17 Division of Critical Care Medicine, St Christopher's Hospital for Children, 3601 A Street, Philadelphia, PA 19134, USA
18 Division of Critical Care Medicine, CS Mott Children's Hospital at the University of Michigan, Ann Arbor, MI 48103, USA
Critical Care 2012, 16:R213 doi:10.1186/cc11847
See related letter by Hamzeh-Cognasse et al., http://ccforum.com/content/17/1/411
Published: 29 October 2012Abstract
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.
