Elevated blood and cerebrospinal fluid biomarkers of microglial activation and blood‒brain barrier disruption in anti-NMDA receptor encephalitis

J Neuroinflammation. 2023 Jul 22;20(1):172. doi: 10.1186/s12974-023-02841-7.

Abstract

Background: Anti-NMDA receptor (NMDAR) encephalitis is an autoimmune disease characterized by complex neuropsychiatric syndrome and cerebrospinal fluid (CSF) NMDAR antibodies. Triggering receptor expressed on myeloid cells 2 (TREM2) has been reported to be associated with inflammation of the central nervous system (CNS). Matrix metalloproteinase-9 (MMP9) and cluster of differentiation (CD44) were measured to evaluate blood‒brain barrier (BBB) permeability in anti-NMDAR encephalitis. The roles of microglial activation and BBB disruption in anti-NMDAR encephalitis are not well known.

Findings: In this work, we detected increased expression levels of CSF sTREM2, CSF and serum CD44, and serum MMP9 in anti-NMDAR encephalitis patients compared with controls. CSF sTREM2 levels were positively related to both CSF CD44 levels (r = 0.702, p < 0.0001) and serum MMP9 levels (r = 0.428, p = 0.021). In addition, CSF sTREM2 levels were related to clinical parameters (modified Rankin Scale scores, r = 0.422, p = 0.023, and Glasgow Coma Scale scores, r = - 0.401, p = 0.031).

Conclusion: Increased sTREM2 levels in CSF as well as increased CD44 and MMP9 in serum and CSF reflected activation of microglia and disruption of the BBB in anti-NMDAR encephalitis, expanding the understanding of neuroinflammation in this disease. The factors mentioned above may have potential as novel targets for intervention or novel diagnostic biomarkers.

Keywords: Anti-NMDA receptor encephalitis; Blood‒brain barrier disruption; CD44; MMP9; Microglial activation; sTREM2.

MeSH terms

  • Anti-N-Methyl-D-Aspartate Receptor Encephalitis*
  • Biomarkers
  • Blood-Brain Barrier*
  • Humans
  • Matrix Metalloproteinase 9
  • Microglia

Substances

  • Matrix Metalloproteinase 9
  • Biomarkers