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外周血结核感染T淋巴细胞斑点试验和脑脊液γ干扰素检测诊断结核性脑膜炎的价值

Performance of peripheral blood T-SPOT.TB and cerebrospinal fluid interferon-γ in the diagnosis of tuberculous meningitis

摘要目的 探讨检测外周血结核感染T细胞斑点试验(T-SPOT.TB)和脑脊液γ干扰素在诊断结核性脑膜炎(TBM)中的价值.方法 从2011年3月至2013年3月复旦大学附属华山医院感染科疑诊为TBM的182例患者中筛选出TBM患者30例(TBM组),对照组为39例非结核性脑膜炎.采用T-SPOT.TB检测外周血结核分枝杆菌抗原特异性分泌γ干扰素的T淋巴细胞;同时采用ELISA法检测脑脊液中未受刺激的γ干扰素含量,TBM组患者治疗4周后复查,观察其动态变化.正态分布的连续变量采用独立样本t检验,非正态分布的样本采用非参数秩和检验.结果 筛选出30例TBM患者,其中6例为确诊病例、24例为疑似病例;对照组39例,包括病毒性脑膜炎12例、化脓性脑膜炎16例、隐球菌性脑膜炎11例.TBM组T-SPOT.TB阳性率为70%(21/30),对照组为13%(5/39),两组差异有统计学意义(x2 =12.15,P<0.01).TBM组首次脑脊液γ干扰素水平中位数为244.35 pg/mL,对照组为9.48 pg/mL,两组差异有统计学意义(Z=-4.646,P<0.01).TBM组有10例患者随访脑脊液γ干扰素水平,治疗后γ干扰素水平中位数为81.36 pg/mL,较治疗前的271.02 pg/mL明显降低,差异有统计学意义(Z=-3.099,P=0.002).外周血T-SPOT.TB诊断TBM的敏感度为70%,特异度为87%;脑脊液γ干扰素诊断TBM的受试者工作特征曲线下面积为0.819,敏感度为83%,特异度为85%.结论 外周血T-SPOT.TB及脑脊液γ干扰素检测对TBM均有较高的诊断价值.动态观察脑脊液γ干扰素含量变化对TBM患者的病情监测具有重要意义.

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abstractsObjective To evaluate the performance of peripheral blood T-SPOT.TB and cerebrospinal fluid (CSF) interferon (IFN)-γ detection in the diagnosis of tuberculous meningitis (TBM).Methods Among the 182 consecutive cases with suspected TBM in Huashan Hospital from March 2011 to March 2013,30 patients were included in the case group according to the latest diagnostic criteria of TBM.Thirty-nine patients diagnosed with non-tuberculous meningitis were included in the control group.T-SPOT.TB was employed to detect tuberculosis-specific IFN-γ-secreting T cells in the peripheral blood.And IFN-γ in CSF was detected simultaneously by enzyme-linked immunosorbent assay (ELISA) without antigen stimulation.The CSF was collected from 10 patients of TBM group after anti tuberculosis treatment for 4 weeks to observe the dynamic changes.The t-test was used for analysis of continuous variables with normal distribution and Kruskal-Wallis test was used for analysis of variables with abnormal distribution.Results ()f the 30 TBM cases,6 were confirmed cases and 24 were highly suspected cases.The control group was comprised of 12 viral encephalitis,16 suppurative meningitis and 11 cryptococcal meningitis.The positive rate of T-SPOT.TB was significantly higher in TBM group compared with control group (70% vs 13%,x2 =12.15,P<0.01).The mean concentration of CSF IFN γ of TBM group was 244.35 pg/mL,which was significantly higher than that of control group 9.48 pg/mL (Z=-4.646,P<0.01).The CSF IFN-γ was significantly decreased after 4 weeks of treatment (271.02 pg/mL vs 81.36 pg/mL,Z=-3.099,P=0.002).The sensitivity and specificity of peripheral blood T-SPOT.TB in the diagnosis of TBM were 70% and 87%,respectively.The area under the receiver operating characteristic (ROC) curve of CSF IFN-γ for TBM diagnosis was 0.819; the optimal cut-off point was 81.36 pg/mL; the corresponding sensitivity and specificity were 83 % and 85 %,respectively.Conclusion Both the detection of peripheral blood T-SPOT.TB and CSF IFN-γ are of great importance for the diagnosis of TBM.Dynamic observation of CSF IFN-γ is important for disease monitoring.

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