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

Abstract

Background Anti-NMDA receptor 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 CNS. Matrix metalloproteinase-9 (MMP9) and the cluster of differentiation (CD44) were measured to evaluate the blood-brain barrier (BBB) permeability of anti-NMDAR encephalitis. The roles of the microglia activation and disruption of BBB in anti-NMDAR encephalitis are not well known. Findings: In this work, we detected the increased expression level of CSF sTREM2, CSF and serum CD44, and serum MMP9 in anti-NMDAR encephalitis patients, compared with control groups. CSF sTREM2 levels were positively related to both the 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 the clinical parameters (mRS scale, r = 0.422, p = 0.023, and GCS scores, r=-0.401, p = 0.031). Conclusion The increased CSF sTREM2 levels and CD44, and MMP9 in serum or CSF showed evidence of the activated microglia and the disruption of BBB in anti-NMDAR encephalitis, expanding the understanding of the neuroinflammation in this disease. These factors mentioned above may be considered novel targets for intervention or novel potential diagnostic biomarkers.