Interleukin-27 as a Sepsis Diagnostic Biomarker in Critically Ill Adults

Abstract

Purpose-We previously identified interleukin-27 (IL-27) as a sepsis diagnostic biomarker in critically ill children. The current study tested the performance of IL-27 alone and in combination with PCT for diagnosing sepsis in critically ill adults.Methods-Serum samples were made available from a prior prospective study of sepsis biomarkers in critically ill adults. The primary analysis used receiver operating characteristic (ROC) curves to evaluate the performance of IL-27 and PCT. Secondary analysis explored IL-27 performance in subgroups of patients with sepsis secondary to lung and non-lung sources of infection. The net reclassification improvement (NRI) was used to estimate the incremental predictive ability of IL-27 compared to PCT alone. Classification and Regression Tree (CART) analysis was used to generate an IL-27-and PCT-based decision tree. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Results-There AUTHOR CONTRIBUTIONSHRW conceived and developed the study, obtained funding for the study, directly took part in the analyses, and wrote the manuscript. CJL collaborated in the initial design of the study and in obtaining funding, oversaw the statistical analyses, and edited the manuscript. PL conducted all biomarker measurements, managed all biological specimens, and edited the manuscript. KWH assisted with statistical analysis and edited the manuscript. SG was the lead investigator for the original study that generated the prospective database used in the current study, assisted with data analysis, and edited the manuscript. All authors read and approved the final manuscript. AUTHOR COMPETING INTERESTSThe remaining authors have no competing interests to report. adding IL-27 to PCT improved discrimination (NRI = 0.685; p < 0.001). The AUC for the CARTderived decision tree was 0.92 (95% CI: 0.88 -0.96) and was significantly greater than that of PCT alone. NIH Public AccessConclusions-When used in combination with PCT, IL-27 may improve classification of critically ill adults with sepsis secondary to a non-lung source of infection.

Performance of interleukin-27 as a sepsis diagnostic biomarker in critically ill adults

“…However, in the secondary analysis a decision tree incorporating rules based on IL-27, PCT, and age reasonably estimated the risk of sepsis in subjects with a non-pulmonary source of sepsis, which is consistent with our previous study in critically ill adults (14). Previous biomarker studies have also demonstrated differences in biomarker performance depending on the source of infection (15), but the biological basis of the discrepancy in the performance of IL-27 between non-pulmonary versus pulmonary causes of sepsis is not evident.…”

“…Based on our prior findings that the performance of IL-27 in adult patients may vary based on the source of sepsis (14), we then analyzed the performance of IL-27 in patients stratified by pulmonary versus non-pulmonary sepsis. Median plasma IL-27 concentrations were higher in the subjects with a non-pulmonary source of sepsis, compared to subjects without sepsis and subjects with a pulmonary source of sepsis (Table 2).…”

“…Because both IL-27 and PCT alone had limited ability to discriminate sepsis from SIRS in this adult cohort, and based on our previous study in critically ill adults with sepsis (14), we next derived a decision tree incorporating IL-27, PCT, and age as potential predictor variables for estimating the risk of non-pulmonary sepsis in patients with SIRS. Age was incorporated based on prior data showing that the performance of diagnostic biomarkers in sepsis may vary by age (23).…”

“…The primary outcome variable for the modeling procedures is sepsis. The secondary outcome variable for the modeling procedure is sepsis from a non-pulmonary source of infection, as in our previous report (14). The CART procedure considered IL-27, PCT, and age as potential predictor variables.…”

“…We subsequently tested the diagnostic performance of IL-27 in an adult cohort and found that a combination of IL-27 and PCT identified critically ill adults with a non-pulmonary source of sepsis more reliably than either biomarker alone (14). This latter observation is consistent with the concept that sepsis diagnostic biomarkers may perform differently depending on the source of infection (15).…”