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

Abstract

IntroductionDifferentiating 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.MethodsGenome-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.ResultsTwo 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.ConclusionsGenome-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.

First characterization of a teleost Epstein-Barr virus-induced gene 3 (EBI3) reveals a regulatory effect of EBI3 on the innate immune response of peripheral blood leukocytes

“…In a recent study, EBI3 was found to be highly expressed in the blood of patients with systemic inflammatory response syndrome, and therefore it was proposed to be a candidate diagnostic biomarker for bacterial infection (Wong et al, 2012). In our study, qRT-PCR analysis showed that under normal physiological conditions, CsE-BI3 expression was most abundant in immune tissues and upregulated in kidney and spleen by E. tarda and megalocytivirus challenge.…”

The Immunobiology of Interleukin-27

“…Multiple reports have shown basal levels of circulating IL-27p28 in humans; these levels are altered in many disease states, including bacterial infections, sepsis, aplastic anemia, and ankylosing spondylitis (167)(168)(169)(170)(171). The interpretation of what the changes in levels of IL-27 mean is not straightforward; increased production could indicate causality or simply be a secondary host response to ongoing disease.…”

Procalcitonin to Detect Suspected Bacterial Infections in the PICU

“…Arkader et al (10) compared 14 patients who were post-cardiopulmonary bypass (CPB) (to emulate SIRS patients) and patients with confirmed bacterial sepsis and concluded that PCT had 83% sensitivity and 93% specificity when using a cutoff of 1.0 ng/mL. Wong et al (11) showed an elevation in PCT in patients with septic shock as compared with patients with SIRS or sepsis. Both of these studies used patients with SIRS as control patients and patients with sepsis as study patients.…”