外周血结核感染T细胞斑点试验及其不同界值水平在结核性胸膜炎中的诊断价值

The diagnostic value of T cell enzyme-linked immuno-spot assay(T-SPOT.TB) on peripheral blood and different thresholds in the tuberculous pleurisy

目的探讨外周血结核感染T细胞斑点试验(T-SPOT.TB)及其不同界值水平在结核性胸膜炎及非结核胸腔积液患者的意义和诊断价值。方法观察40例结核性胸膜炎患者(包括16例病理确诊患者和24例临床诊断患者)及13例非结核胸腔积液患者,进行外周血T-SPOT.TB测定,应用SPSS19.0对TSPOT.TB斑点形成细胞(SFC)(个/106)进行统计学分析。结果结核性胸膜炎组的外周血T-SPOT.TB阳性率为85.0%,显著高于非结核性胸腔积液组的23.1%(P<0.01);结核性胸膜炎组的外周血抗原A(ESAT-6抗原)和抗原B(CFP-10抗原)的SFC分别为[15.2(0~110)/106]和[52.0(0~200)/106],明显高于非结核胸腔积液组[分别为0.5(0~40)/106和1.0(0~52)/106](P均<0.05)。应用受试者工作特征(ROC)曲线对结核性胸膜炎组分析结果显示,ESAT-6抗原和CFP-10抗原的SFC数值在ROC曲线下面积(AUC)分别为0.842和0.880,AUC的95%可信区间分别为(0.782~0.967)和(0.771~0.977)(P均<0.05)。根据约登指数确定ESAT-6抗原和CFP-10抗原的诊断界值水平,将ESAT-6抗原为6/106<SFC<48.5/106时定义为弱阳性,其特异度为92.3%;将ESAT-6抗原的SFC≥48.5/106时定义为强阳性,其特异度可达100.0%;将CFP-10抗原为6/106<SFC<57/106时定义为弱阳性,其特异度为84.6%;当CFP-10抗原的SFC≥57/106时定义为强阳性,其特异度为100.0%。将临床诊断组与病理确诊组患者T-SPOT.TB的ESAT-6抗原和CFP-10抗原弱阳性率及强阳性率比较发现,两组抗原的弱阳性率比较差异均无统计学意义(P>0.05),而病理确诊组患者ESAT-6抗原和CFP-10抗原强阳性率均高于临床诊断组(P<0.05)。结论外周血T-SPOT.TB在结核性胸膜炎诊断中具有较高的阳性率和较好的诊断效率,ESAT-6抗原和(或)CFP-10抗原的SFC数值在高界值水平则强烈提示为活动性结核感染。观测外周血T-SPOT.TB的ESAT-6抗原和(或)CFP-10抗原的界值水平及SFC数值高低在结核性胸膜炎诊断中具有重要的价值和意义。

Objective To explore the value of T cell enzyme-linked immuno-spot assay（T-SPOT.TB） on peripheral blood and different thresholds in the diagnosis of tuberculous pleurisy and non- tuberculous pleurisy.Methods A total of 40 cases were enrolled in this study among whom 16 cases were classified as pathologically diagnosed tuberculous pleurisy, and the other 24 cases were classified as clinically diagnosed tuberculous pleurisy. Other 13 cases with non- tuberculous pleurisy were taken as the control group. The peripheral blood of all the patients was tested by T-SPOT.TB and the results were analyzed by SPSS 19.0 according to the spot forming cells（SFCs）.Results Compared with that in non- tuberculous pleurisy, the positive rate of T-SPOT.TB in tuberculous pleurisy was higher（23.1% vs 85.0%, P〈0.01）. The SFCs of peripheral blood antigen A（ESAT-6 antigen） and antigen B（CFP-10 antigen） were greater in the tuberculous pleurisy group[15.2（0～110）/10^6 and 52.0（0～200）/10^6, respectively] than those in the non- tuberculous pleurisy group[0.5（0～40） /106 and 1.0（0～52）/10^6, respectively]（P〈0.05）. In tuberculous pleurisy, the areas under the receiver operating characteristic（ROC） curve（AUS） of ESAT-6 and CFP-10 were 0.842 and 0.880, respectively. In addition, AUC 95% confidence intervals were （0.782～0.967） and （0.771～0.977）, respectively（P〈0.05）. Different cut-off points of Jouden Index were used to classify ESAT-6 antigen and CFP-10 antigen thresholds in the diagnosis of tuberculous pleurisy. If ESAT-6 antigen diagnosis cut-off value was weakly positive（6/106 6）, the specificity was 92.3%. However, if it was strongly positive（SFC≥48.5/106）, the specificity was 100.0%. For CFP-10 antigen, if there was（6/106 6）, the specificity was 84.6%. However, if it was strongly positive（SFC≥57/106）, the specificity was 100.0%. The weakly positive rates of ESAT-6 antigen and CFP-10 antigen were no significantly different between the pathological diagnosed groups and the clinically diagnosed groups. However, compared with those in the clinically diagnosed groups, the strongly positive rates of ESAT-6 antigen and CFP-10 antigen were greater than those in the pathological diagnosed groups.Conclusion Peripheral blood T-SPOT.TB can improve the diagnostic performance for tuberculous pleurisy. The SFC values of ESAT-6 antigen and/or CFP-10 in high cut-off level indicate that tuberculosis infection is active. It is of great value and significance to detect the different threshold values and SFC of ESAT-6 antigen and/or CFP-10 antigen in the diagnosis of tuberculous pleurisy.