title: Interleukin-27 is a novel candidate diagnostic biomarker for bacterial infection in critically ill children.
abstract: BACKGROUND
  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.
authors.forename: Hector R
authors.initials: HR
authors.lastname: Wong
authors.forename: Natalie Z
authors.initials: NZ
authors.lastname: Cvijanovich
authors.forename: Mark
authors.initials: M
authors.lastname: Hall
authors.forename: Geoffrey L
authors.initials: GL
authors.lastname: Allen
authors.forename: Neal J
authors.initials: NJ
authors.lastname: Thomas
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Freishtat
authors.forename: Nick
authors.initials: N
authors.lastname: Anas
authors.forename: Keith
authors.initials: K
authors.lastname: Meyer
authors.forename: Paul A
authors.initials: PA
authors.lastname: Checchia
authors.forename: Richard
authors.initials: R
authors.lastname: Lin
authors.forename: Michael T
authors.initials: MT
authors.lastname: Bigham
authors.forename: Anita
authors.initials: A
authors.lastname: Sen
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Nowak
authors.forename: Michael
authors.initials: M
authors.lastname: Quasney
authors.forename: Jared W
authors.initials: JW
authors.lastname: Henricksen
authors.forename: Arun
authors.initials: A
authors.lastname: Chopra
authors.forename: Sharon
authors.initials: S
authors.lastname: Banschbach
authors.forename: Eileen
authors.initials: E
authors.lastname: Beckman
authors.forename: Kelli
authors.initials: K
authors.lastname: Harmon
authors.forename: Patrick
authors.initials: P
authors.lastname: Lahni
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Shanley
mesh_terms: D015415:Biomarkers / Q000097:blood; D002116:Calcitonin / Q000097:blood; D015740:Calcitonin Gene-Related Peptide; D002675:Child, Preschool; D016638:Critical Illness; D005260:Female; D015870:Gene Expression; D006801:Humans; D007223:Infant; D007378:Interleukins / Q000097:blood*; D008297:Male; D046228:Microarray Analysis; D011237:Predictive Value of Tests; D011498:Protein Precursors / Q000097:blood; D012680:Sensitivity and Specificity; D018805:Sepsis / Q000175:diagnosis*; D018746:Systemic Inflammatory Response Syndrome / Q000175:diagnosis
chemical_list: D015415:Biomarkers; C000606589:CALCA protein, human; D007378:Interleukins; C464565:MYDGF protein, human; D011498:Protein Precursors; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide