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.

B7-H3 Augments the Inflammatory Response and Is Associated with Human Sepsis

“…Our previous work has shown that sB7-H3, released from monocytes, dendritic cells, and activated T cells, is detectable in the circulation of healthy humans (19). We also found that markedly increased levels of sB7-H3 were present in the serum samples from patients with bacterial meningitis when compared with healthy controls or patients with aseptic meningitis (23). In this study, we further demonstrated that patients diagnosed with sepsis, in contrast to healthy individuals, exhibited significantly elevated levels of sB7-H3 in their plasma, and more importantly, that plasma levels of sB7-H3 observed in the nonsurvivors of septic patients were substantially higher than those observed in the survivors.…”

Costimulatory Protein 4IgB7H3 Drives the Malignant Phenotype of Glioblastoma by Mediating Immune Escape and Invasiveness

“…Interestingly, native glioblastoma-derived soluble 4IgB7H3 suppresses NK lysis and enhances glioblastoma cell invasiveness in vitro. Insofar, our data let us to postulate that NK cell suppression and the proinvasive effect attributed to 4IgB7H3 expression in different tumor entities (37) are in fact exerted by membrane-bound and soluble B7H3, which was until now only evaluated for its diagnostic and prognostic capacity (22,23,38). Finally, as soluble 4IgB7H3 was sufficient to restore the invasiveness of 4IgB7H3-silenced LN-229 cells, the presence of a yet unknown counter-receptor must be postulated on glioblastoma cells, too.…”

B7-H3 Participates in the Development of Experimental Pneumococcal Meningitis by Augmentation of the Inflammatory Response via a TLR2-Dependent Mechanism

“…Our recent clinical study did show significantly elevated levels of sB7-H3 in the circulation and cerebrospinal fluid of patients diagnosed with bacterial meningitis (23). Levels of cerebrospinal fluid and plasma sB7-H3 in these patients correlate with the intensity of their infectious inflammatory process and may also act as a useful marker for distinguishing bacterial from aseptic meningitis.…”