结核分枝杆菌特异性抗原反应性因子对活动性肺结核的鉴别诊断意义

The potential value of mtb-specific-antiqen induced factors as biomarkers for the differential diagnosis of active pulmonary tuberculosis

目的研究活动性肺结核和细菌性肺炎及原发性支气管肺癌患者的外周血单个核细胞（PBMCs）经结核分枝杆菌特异性抗原肽刺激后的多因子表达特点及诊断意义。方法 100例初治活动性肺结核患者,35例细菌性肺炎和原发性支气管肺癌患者,分离外周血单个核细胞（PBMCs）,用结核分枝杆菌特异性抗原肽刺激,采用FlowCytomix流式技术检测细胞培养液上清上中IFN-γ、TNF-α、IL-2、IP-10（CXCL10）和MIG（CXCL9）的表达,用接受者工作特征曲线（ROC curve）评价以上结核分枝杆菌抗原特异反应性因子的诊断价值。结果 PBMCs经结核分枝杆菌特异性抗原肽刺激后,培养液上清中IFN-γ、TNF-α、IL-2、IP-10和MIG水平显著升高,初治活动性肺结核患者与其他肺病对照组差别显著（中位值分别为595.0/0.0 pg/ml,338.0/48.6 pg/ml,226.0/0.0 pg/ml,3 865.0/297.0 pg/ml,3541.0/81.1 pg/ml;P值均〈0.000 1）,ROC曲线下面积（95%CI）分别为0.917 1（0.862 9~0.971 4）,0.807 0（0.724 6~0.889 4）,0.854 9（0.785 5~0.924 2）,0.920 0（0.870 8~0.969 2）,0.936 3（0.894 4~0.978 1）,IFN-γ诊断特异性为94.3%,联合IP-10诊断提高敏感性至92.1%。结论结核分枝杆菌特异性抗原肽刺激外周血单个核细胞产生的MIG、IP-10和IFN-γ能够良好的鉴别初治活动性肺结核及常见的细菌性肺炎和原发性支气管肺癌,可能成为新的诊断指标。

It is difficult to differentiate pulmonary tuberculosis with negative Mtb sputum from bacterial pneumonia and primary lung cancer.Some induced cytokines from PBMCs stimulated with specific Mtb antigens have found to be different between active pulmonary tuberculosis and latent tuberculosis infection.In this study,100 patients with newly-treated active pulmonary tuberculosis,35 patients with bacterial pneumonia and primary lung cancer were enrolled to study the potential value of induced IFN-γ,TNF-α,IL-2,IP-10（CXCL10） and MIG（CXCL9） in supernatants of PBMCs stimulated with Mycobacterium tuberculosis-specific antigens in the differential diagnosis.The samples were analyzed with eBioscience FlowCytomix on flow cytometry.The diagnostic values were evaluated based on receiver operating characteristic（ROC） curve analysis.Result showed that PBMCs stimulated with Mtb-specific antigens produced significantly higher levels of IFN-γ,TNF-α,IL-2,IP-10 and MIG in active pulmonary TB patients than in controls（P 0.000 1）.MIG possessed the highest area under ROC curve,and the specificity of IFN-γ was up to 94.3%.By combining IP-10 and IFN-γ tests,the sensitivity was increased to 92.1%.So the MIG,IP-10 and IFN-γ responses to Mtb-specific antigens could be used to discriminate newly-treated active pulmonary tuberculosis from bacterial pneumonia and primary lung cancer.In conclusion,combining MIG,IP-10 and IFN-γ may be a simple and quick approach to diagnosis newly-treated active pulmonary tuberculosis.