Circulating B7-H3(CD276) Elevations in Cerebrospinal Fluid and Plasma of Children with Bacterial Meningitis

Abstract

The objective of this study was to analyze the clinical significance of cerebrospinal fluid (CSF) and plasma concentrations of B7-H3, tumor necrosis factor-alpha (TNF-alpha), gamma interferon (IFN-gamma), and interleukin-17 (IL-17) in bacterial and aseptic meningitis in children. The participants were six children with bacterial meningitis, 16 with aseptic meningitis, and 12 control subjects. All participants were between 2 months and 12 years of age on admission. Cytokines determination was performed by enzyme-linked immunosorbent assay technique. CSF and plasma-circulating B7-H3 were significantly higher in the bacterial meningitis group as compared with the aseptic group (p = 0.001) and the control group (p = 0.000 and p = 0.001 respectively). However, CSF and plasma-circulating B7-H3 in aseptic meningitis were not significantly higher than control group (p = 0.071 and p = 0.72 respectively).CSF and plasma-circulating TNF-alpha were significantly higher in the bacterial meningitis group as compared with the aseptic group (p = 0.004 and p < 0.0001 respectively) and control group (p = 0.004 and p < 0.0001 respectively). Similarly, we did not observe significant elevated TNF-alpha levels in CSF and plasma in aseptic group compared with control group (p = 0.03 and p = 0.12 respectively). IFN-gamma levels in CSF and plasma were undetectable in control group, and we did not find statistical significances in both of CSF and plasma between the elevated IFN-gamma level in bacterial meningitis group and aseptic meningitis group(p = 0.055 and p = 0.095 respectively) CSF and plasma levels of IL-17 were undetectable in all subjects. There were correlations between B7-H3 and TNF-alpha, IFN-gamma (r = 0.875, p = 0.000; r = -0.693, p = 0.000, respectively) in CSF in meningitis subjects. In plasma, levels of B7-H3 in bacterial meningitis on admission correlated positively with TNF-alpha (r = 0.968, p = 0.002), and white blood cell counts (r = 0.973, p = 0.001). Detectable CSF levels of B7-H3, TNF-alpha, and IFN-gamma on admission were not associated significantly with any of CSF characteristics. Additionally, CSF and plasma levels of B7-H3 decreased remarkably after treatment. Altogether, our data indicated that circulating B7-H3 and TNF-alpha levels in the CSF and plasma were useful markers for distinguishing bacterial from aseptic meningitis, and Circulating B7-H3 was demonstrated to be useful in evaluating the intensity of the infectious inflammatory process in the central nervous system in children.