外周血及脑脊液结核感染T淋巴细胞斑点试验对结核性脑膜炎的诊断价值

Diagnostic value of T cells spot test of tuberculosis infection on blood and cerebrospinal fluid for tuberculous meningitis

目的评价外周血及脑脊液结核感染T淋巴细胞斑点试验(T cells spot test of tuberculosis infection,T-SPOT.TB)对结核性脑膜炎的诊断价值。方法2013年3月至2017年3月复旦大学附属华山医院临床疑似结核性脑膜炎患者115例,最终确诊为结核性脑膜炎患者30例,非结核性感染性脑膜炎患者37例,非感染性脑膜炎患者29例。采用Fisher确切概率法评价外周血及脑脊液T-SPOT.TB的敏感度、特异度、阳性预测值、阴性预测值,采用受试者工作特征(receiver operating characteristic curve,ROC)曲线下面积(area under the curve,AUC)评估外周血及脑脊液T-SPOT.TB的诊断效能。结果30例结核性脑膜炎和66例非结核性脑膜炎患者外周血T-SPOT.TB的敏感度、特异度、阳性预测值、阴性预测值分别为93.1%、77.0%、65.9%和95.9%,脑脊液T-SPOT.TB分别为66.7%、87.7%、71.4%和85.1%。30例结核性脑膜炎和37例其他感染性脑膜炎患者外周血T-SPOT.TB的敏感度、特异度、阳性预测值、阴性预测值分别为93.1%、68.6%、71.1%和92.3%,脑脊液T-SPOT.TB分别为66.7%、86.5%、80.0%和76.2%。外周血及脑脊液T-SPOT.TB的AUC分别为0.882(95%CI:0.795~0.969)和0.814(95%CI:0.704~0.925)。脑脊液T-SPOT.TB诊断结核性脑膜炎的临界值为8SFC/2.5×105个细胞时,脑脊液T-SPOT.TB的敏感度为66.7%,特异度为91.9%,阳性预测值为87.0%,阴性预测值为77.3%,阳性似然比达8.22,阴性似然比为0.363。结论脑脊液T-SPOT.TB对结核性脑膜炎有一定的诊断价值,且8SFC/2.5×105个细胞可能是区分结核和非结核性脑膜炎的参考临界值。

Objective To evaluate the diagnostic value of T cells spot test of tuberculosis infection (T-SPOT.TB) on blood and cerebrospinal fluid for tuberculous meningitis (TBM). Methods One hundred and fifteen adult patients with suspected tuberculous meningitis were retrospectively enrolled from March 2013 to March 2017 in Huashan Hospital affiliated to Fudan University. Among them, 30 were diagnosed with TBM (7 definite, 19 highly probable and 4 possible), 37 with other infectious meningitis and 29 with non-infectious meningitis. The diagnostic sensitivity, specificity, positive predictive values (PPV) and negative predictive values (NPV) of T-SPOT.TB on peripheral mononuclear cells (PBMC) and cerebrospinal fluid mononuclear cells (CSF-MC) were analyzed using Fisher exact test, and the diagnostic performance was evaluated by using receiver operating characteristic (ROC) curve and area under the curve (AUC). Results When including the 30 TBM cases and 66 non-TBM cases into analysis, the sensitivities and specificities, PPV and NPV of PBMC and CSF-MC for diagnosing TBM were as follows: 93.1% and 66.7%, 77% and 87.7%, 65.9% and 71.4%, 95.9% and 85.1%, respectively. When including the 30 TBM and 37 other infectious meningitis into analysis, the sensitivities and specificities, PPV and NPV of the PBMC and CSF-MC for diagnosing TBM were as follows: 93.1% and 66.7%, 68.6% and 86.5%, 71.1% and 80.0%, 92.3% and 76.2%, respectively. By ROC curve analysis, the AUC of blood and CSF were 0.882 (95%CI: 0.795-0.969) and 0.814 (95% CI: 0.704-0.925), respectively. Using a cut-off value of 32 spot forming cells (SFC) per million CSF-MC for T-SPOT.TB on CSF-MC showed a sensitivity of 66.7%, a specificity of 91.9%, PPV of 87.0% and NPV of 77.3%. The positive likelihood ratio and negative likelihood ratio were 8.22 and 0.363 respectively. Conclusions T-SPOT.TB on CSF-MC has a role in diagnosing TBM. And 32 SFC per million CSF-MC might be the optimal cut-off value to differentiate TBM and non-TBM.