结核性脑膜炎临床特征及脑脊液β2-MG、ADA、MMP-9、MMP-9/TIMP-1表达检测的诊断价值

Clinical features and diagnostic values of cerebrospinal fluid β2-MG, ADA, MMP-9, MMP-9/TIMP-1 in tuberculous meningitis

  • 摘要:
    目的 探讨结核分枝杆菌感染所致结核性脑膜炎(TBM)患者的临床特征及脑脊液β2微球蛋白(β2-MG)、腺苷脱氨酶(ADA)、基质金属蛋白酶9(MMP-9)、MMP-9/基质金属蛋白酶组织抑制剂1(TIMP-1)表达检测的临床意义。
    方法 选取2021年10月-2024年4月贵阳市公共卫生救治中心、贵阳市第一人民医院、贵阳市妇幼保健院收治的脑膜炎患者208例, 根据临床最终诊断结果分为TBM组(84例), 化脓性脑膜炎(PM)组(61例), 病毒性脑膜炎(VM)组(63例); 根据病情严重程度将TBM组患者分为Ⅰ期组(33例), Ⅱ期组(30例), Ⅲ期组(21例)。比较TBM组、PM组、VM组脑脊液β2-MG、ADA、MMP-9、MMP-9/TIMP-1表达水平, 比较不同病情严重程度组脑脊液β2-MG、ADA、MMP-9、MMP-9/TIMP-1表达水平, 分析脑脊液β2-MG、ADA、MMP-9、MMP-9/TIMP-1表达水平与病情严重程度的相关性, 分析脑脊液β2-MG、ADA、MMP-9、MMP-9/TIMP-1表达水平单独及联合检测对结核分枝杆菌感染所致TBM的诊断价值。
    结果 TBM组、PM组脑脊液β2-MG、ADA、MMP-9、MMP-9/TIMP-1表达水平高于VM组, 且TBM组高于PM组(P<0.05)。Ⅲ期组、Ⅱ期组脑脊液β2-MG、ADA、MMP-9、MMP-9/TIMP-1表达水平高于Ⅰ期组, 且Ⅲ期组高于Ⅱ期组(P<0.05)。脑脊液β2-MG、ADA、MMP-9、MMP-9/TIMP-1表达水平与病情严重程度呈正相关(P<0.05)。脑脊液β2-MG、ADA、MMP-9、MMP-9/TIMP-1表达水平联合检测对结核分枝杆菌感染所致TBM的诊断曲线下面积(AUC)值高于单独检测的AUC值(P<0.05), 且联合检测的敏感度为84.52%, 特异度为95.08%。
    结论 脑脊液β2-MG、ADA、MMP-9、MMP-9/TIMP-1表达水平变化与TBM及PM有关, 且与TBM患者病情严重程度相关, 四者联合检测对结核分枝杆菌感染所致TBM诊断价值较高。

     

    Abstract:
    OBJECTIVE To explore the clinical characteristics of tuberculous meningitis (TBM) caused by Mycobacterium tuberculosis and the clinical significance of β2-microglobulin (β2-MG), adenosine deaminase (ADA), matrix metalloproteinase 9(MMP-9) and MMP-9/ tissue inhibitor of metalloproteinase 1(TIMP-1) in cerebrospinal fluid.
    METHODS Totally 208 cases of meningitis admitted to Guiyang Public Health Treatment Center, Guiyang First People′s Hospital and Guiyang Maternal and Child Health Care Hospital from Oct. 2021 to Apr. 2024 were divided into the TBM group (n=84), purulent meningitis (PM) group (n=61) and viral meningitis (VM) group (n=63) according to the final clinical diagnosis. Based on the severity, TBM patients were divided into three groups: the stage Ⅰ(n=33), Ⅱ (n=30) and Ⅲ group (n=21). The levels of β2-MG, ADA, MMP-9, MMP-9/TIMP-1 among different groups were compared, their correlations with the disease severity and diagnostic values for TBM caused by M. tuberculosis were analyzed.
    RESULTS Among the TBM, PM and VM group, the levels of β2-MG, ADA, MMP-9 and MMP-9/TIMP-1 in cerebrospinal fluid of the TBM group were the highest, followed by the PM and VM group (P < 0.05). Among the stage Ⅰ, Ⅱ and Ⅲ group, the levels of β2-MG, ADA, MMP-9, MMP-9/TIMP-1 in cerebrospinal fluid of the stage Ⅲ group were the highest, followed by stage Ⅱ and Ⅰ group (P < 0.05). The levels of β2-MG, ADA, MMP-9 and MMP-9/TIMP-1 in cerebrospinal fluid were positively correlated with the severity of the disease (P < 0.05). The area under the diagnostic curve (AUC) of the combination of β2-MG, ADA, MMP-9 and MMP-9/TIMP-1 in cerebrospinal fluid was higher than that of single detection for TBM caused by M. tuberculosis (P < 0.05), with the sensitivity and specificity 84.52% and 95.08%, respectively.
    CONCLUSIONS The levels of β2-MG, ADA, MMP-9, MMP-9/TIMP-1 in cerebrospinal fluid are related to the occurrence of TBM and PM, even to the severity of TBM. The combined detection of the four indices has relatively high diagnostic value for TBM caused by M. tuberculosis.

     

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