Department of Neurology, Neuroinfection and Neuroimmunology Center, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China.
China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China.
J Neuroinflammation. 2023 Jul 22;20(1):172. doi: 10.1186/s12974-023-02841-7.
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.
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).
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.
抗 N- 甲基-D- 天冬氨酸受体(NMDAR)脑炎是一种自身免疫性疾病,其特征为复杂的神经精神综合征和脑脊液(CSF)NMDAR 抗体。髓样细胞触发受体 2(TREM2)已被报道与中枢神经系统(CNS)炎症有关。基质金属蛋白酶-9(MMP9)和分化群(CD44)用于评估抗 NMDAR 脑炎的血脑屏障(BBB)通透性。小胶质细胞激活和 BBB 破坏在抗 NMDAR 脑炎中的作用尚不清楚。
在这项工作中,与对照组相比,我们检测到抗 NMDAR 脑炎患者的 CSF sTREM2、CSF 和血清 CD44 以及血清 MMP9 的表达水平升高。CSF sTREM2 水平与 CSF CD44 水平呈正相关(r=0.702,p<0.0001),与血清 MMP9 水平呈正相关(r=0.428,p=0.021)。此外,CSF sTREM2 水平与临床参数(改良 Rankin 量表评分,r=0.422,p=0.023,和格拉斯哥昏迷量表评分,r=-0.401,p=0.031)相关。
CSF 中 sTREM2 水平升高,以及血清和 CSF 中 CD44 和 MMP9 水平升高,反映了抗 NMDAR 脑炎中小胶质细胞的激活和 BBB 的破坏,扩大了对该疾病神经炎症的认识。上述因素可能具有作为新的干预靶点或新的诊断生物标志物的潜力。