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

Shock. 2017 Feb;47(2):140-147. doi: 10.1097/SHK.0000000000000753.

Abstract

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-1β, 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-1β 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.

MeSH terms

  • Biomarkers / blood*
  • C-Reactive Protein / metabolism
  • Calcitonin / blood
  • Chemokine CCL3 / blood
  • Chemokine CCL4 / blood
  • Female
  • Granzymes / blood
  • HSP70 Heat-Shock Proteins / blood
  • Humans
  • Infant, Newborn
  • Interleukin-6 / blood
  • Interleukin-8 / blood
  • Interleukins / blood*
  • Male
  • Matrix Metalloproteinase 8 / blood
  • Neonatal Sepsis / blood*
  • Neonatal Sepsis / diagnosis*
  • ROC Curve
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Biomarkers
  • Chemokine CCL3
  • Chemokine CCL4
  • HSP70 Heat-Shock Proteins
  • Interleukin-6
  • Interleukin-8
  • Interleukins
  • MYDGF protein, human
  • Tumor Necrosis Factor-alpha
  • Calcitonin
  • C-Reactive Protein
  • Granzymes
  • Matrix Metalloproteinase 8