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

Hector R. Wong, Natalie Z. Cvijanovich, Mark Hall, Geoffrey L. Allen, Neal J. Thomas, Robert J. Freishtat, Nick Anas, Keith Meyer, Paul A. Checchia, Richard Lin, Michael T. Bigham, Anita Sen, Jeffrey Nowak, Michael Quasney, Jared W. Henricksen, Arun Chopra, Sharon Banschbach, Eileen Beckman, Kelli Harmon, Patrick LahniThomas P. Shanley

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Article numberR213
JournalCritical Care
Volume16
Issue number5
DOIs
StatePublished - Oct 26 2012

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Interleukin-27
Systemic Inflammatory Response Syndrome
Bacterial Infections
Critical Illness
Biomarkers
Sepsis
Calcitonin
Genome
Human Herpesvirus 4
Genes
Infection
Serum
Gene Expression
Decision Trees
Computer-Assisted Image Processing
Routine Diagnostic Tests
Proteins
Fever
Databases
Cytokines

All Science Journal Classification (ASJC) codes

  • Critical Care and Intensive Care Medicine

Cite this

Wong, H. R., Cvijanovich, N. Z., Hall, M., Allen, G. L., Thomas, N. J., Freishtat, R. J., ... Shanley, T. P. (2012). Interleukin-27 is a novel candidate diagnostic biomarker for bacterial infection in critically ill children. Critical Care, 16(5), [R213]. https://doi.org/10.1186/cc11847
Wong, Hector R. ; Cvijanovich, Natalie Z. ; Hall, Mark ; Allen, Geoffrey L. ; Thomas, Neal J. ; Freishtat, Robert J. ; Anas, Nick ; Meyer, Keith ; Checchia, Paul A. ; Lin, Richard ; Bigham, Michael T. ; Sen, Anita ; Nowak, Jeffrey ; Quasney, Michael ; Henricksen, Jared W. ; Chopra, Arun ; Banschbach, Sharon ; Beckman, Eileen ; Harmon, Kelli ; Lahni, Patrick ; Shanley, Thomas P. / Interleukin-27 is a novel candidate diagnostic biomarker for bacterial infection in critically ill children. In: Critical Care. 2012 ; Vol. 16, No. 5.
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abstract = "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.",
author = "Wong, {Hector R.} and Cvijanovich, {Natalie Z.} and Mark Hall and Allen, {Geoffrey L.} and Thomas, {Neal J.} and Freishtat, {Robert J.} and Nick Anas and Keith Meyer and Checchia, {Paul A.} and Richard Lin and Bigham, {Michael T.} and Anita Sen and Jeffrey Nowak and Michael Quasney and Henricksen, {Jared W.} and Arun Chopra and Sharon Banschbach and Eileen Beckman and Kelli Harmon and Patrick Lahni and Shanley, {Thomas P.}",
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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 2012, 'Interleukin-27 is a novel candidate diagnostic biomarker for bacterial infection in critically ill children', Critical Care, vol. 16, no. 5, R213. https://doi.org/10.1186/cc11847

Interleukin-27 is a novel candidate diagnostic biomarker for bacterial infection in critically ill children. / Wong, Hector R.; Cvijanovich, Natalie Z.; Hall, Mark; Allen, Geoffrey L.; Thomas, Neal J.; Freishtat, Robert J.; Anas, Nick; Meyer, Keith; Checchia, Paul A.; Lin, Richard; Bigham, Michael T.; Sen, Anita; Nowak, Jeffrey; Quasney, Michael; Henricksen, Jared W.; Chopra, Arun; Banschbach, Sharon; Beckman, Eileen; Harmon, Kelli; Lahni, Patrick; Shanley, Thomas P.

In: Critical Care, Vol. 16, No. 5, R213, 26.10.2012.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Interleukin-27 is a novel candidate diagnostic biomarker for bacterial infection in critically ill children

AU - Wong, Hector R.

AU - Cvijanovich, Natalie Z.

AU - Hall, Mark

AU - Allen, Geoffrey L.

AU - Thomas, Neal J.

AU - Freishtat, Robert J.

AU - Anas, Nick

AU - Meyer, Keith

AU - Checchia, Paul A.

AU - Lin, Richard

AU - Bigham, Michael T.

AU - Sen, Anita

AU - Nowak, Jeffrey

AU - Quasney, Michael

AU - Henricksen, Jared W.

AU - Chopra, Arun

AU - Banschbach, Sharon

AU - Beckman, Eileen

AU - Harmon, Kelli

AU - Lahni, Patrick

AU - Shanley, Thomas P.

PY - 2012/10/26

Y1 - 2012/10/26

N2 - 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.

AB - 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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