Cytokine profiles as novel diagnostic markers of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis in children

J Crit Care. 2017 Jun:39:72-77. doi: 10.1016/j.jcrc.2017.02.018. Epub 2017 Feb 10.

Abstract

Purpose: The aim of this study was to identify specific laboratory indices to distinguish Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) in children.

Materials and methods: In this prospective study, Th1/Th2 cytokines, including IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ, were analyzed in patients with EBV-HLH or sepsis at the onset of disease by flow cytometry.

Results: IL-10, IFN-γ, IL-10/IL-6, and IFN-γ/IL-6 were higher and IL-6 was lower in EBV-HLH patients compared to sepsis patient levels. When using the criteria of IL-10 >20.9 pg/mL, IFN-γ >17.9 pg/mL, IL-10/IL-6 >0.5 and IFN-γ/IL-6 >0.7, the sensitivity was 89.8%, 93.2%, 93.2%, and 91.5%, while the specificity was 89.8%, 100%, 94.9%, and 100%, respectively. After treatment of EBV-HLH patients, IL-6, IL-10, TNF-α, and IFN-γ were significantly reduced (IL-6: P<.001; IL-10: P<.001; TNF-α: P=.011; IFN-γ: P<.001).

Conclusions: This study showed that IFN-γ, IL-10/IL-6, and IFN-γ/IL-6 are novel specific indicators for differential diagnosis of EBV-HLH. Additionally, IL-6, IL-10, TNF-α, and IFN-γ are useful indices for monitoring the effects of treatment on EBV-HLH.

Keywords: Cytokines; EBV-HLH; IFN-γ/Il-6; Il-10/Il-6.

MeSH terms

  • Biomarkers / metabolism
  • Child
  • Child, Preschool
  • Cytokines / metabolism*
  • Epstein-Barr Virus Infections / diagnosis*
  • Female
  • Flow Cytometry
  • Herpesvirus 4, Human
  • Humans
  • Infant
  • Interleukins / metabolism
  • Lymphohistiocytosis, Hemophagocytic / diagnosis*
  • Lymphohistiocytosis, Hemophagocytic / virology
  • Male
  • Prospective Studies
  • Sensitivity and Specificity
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Biomarkers
  • Cytokines
  • Interleukins
  • Tumor Necrosis Factor-alpha