Multiplex Cytokine Profiling Identifies Interleukin-27 as a Novel Biomarker For Neonatal Early Onset Sepsis.

BACKGROUND: Early onset sepsis (EOS) remains a major cause of mortality and morbidity in neonates, and traditional clinical markers effective for adults are less effective in these patients. This study aimed to assess the value of individual plasma biomarkers as well as biomarker combinations for predicting EOS in neonates. METHODS: This prospective study included 151 neonates with suspected EOS. Plasma levels of interleukin (IL)-27, IL-6, IL-8, tumor necrosis factor (TNF)-α, heat shock protein (HSP) 70, macrophage inflammatory protein (MIP)-1α, MIP-1ß, granzyme B, and matrix metalloproteinase (MMP)-8 were measured through multiplex cytokine profiling and assessed along with C-reactive protein (CRP) and procalcitonin (PCT). Receiver operating characteristic (ROC) curve analysis was performed to evaluate the predictive ability of biomarkers individually and in combination. Logistic regression model was constructed to identify independent predictors of EOS. RESULTS: The proven sepsis and probable sepsis groups were combined to form the infected group (n = 68), and the possible sepsis and low-risk sepsis groups were combined to form the uninfected group (n = 83). The ROC area under the curve was 0.747 for IL-27 (P <0.01). In addition, IL-6, TNF-α, HSP 70, MMP-8, PCT, and CRP were significantly predictive of EOS, whereas IL-8, granzyme B, MIP-1α, and MIP-1ß were not. Both IL-27 and PCT were identified as independent predictors of EOS in the multivariate model, and the combined use of these markers showed significantly increased predictive ability for EOS. CONCLUSION: Our results indicate that elevated IL-27 strongly correlates with EOS and may provide additional diagnostic value along with PCT.

Interleukin 35: A novel candidate biomarker to diagnose early onset sepsis in neonates.

BACKGROUND: Early onset sepsis (EOS) remains a major cause of morbidity and mortality in newborns; however, current diagnostic tools are inadequate. We evaluated the accuracy of a novel cytokine, interleukin (IL)-35, for the diagnosis of EOS in comparison with other infection markers. METHODS: One hundred fifty-seven neonates with suspected sepsis in the first 3days of life were enrolled in this perspective study. All enrolled patients were divided into infected group and unlikely infected group according to clinical data. IL-35, C-reactive protein (CRP), procalcitonin (PCT), white blood cell (WBC) count, and blood culture were measured once the suspected EOS was documented. RESULTS: Serum concentration of IL-35 was increased significantly in the infected group compared with the unlikely infected group (median 36.4 versus 27.1pg/ml, respectively, p<0.001). The area under receiver-operating characteristic (ROC) curve were 0.756 for IL-35, 0.713 for PCT (age-adjusted), 0.670 for CRP, and 0.619 for WBC. With a cut-off value of 31.7pg/ml, the diagnostic sensitivity and specificity of IL-35 were 78.48% and 66.67%, respectively. Moreover, unlike PCT concentration, IL-35 concentration did not fluctuate in neonates who were unlikely to be infected (p=0.885). CONCLUSION: The diagnostic performance of IL-35 was superior to that of PCT and other commonly used markers, suggesting that IL-35 may be a valuable tool for EOS diagnosis.