摘要目的 探讨结核感染T细胞斑点试验(T-SPOT)中结核特异性抗原(TBAg)和植物血凝素(PHA)比值(TBAg/PHA)对活动性结核的诊断价值.方法 纳入2014年1月至2017年1月华中科技大学同济医学院附属同济医院MTB培养阳性患者378例,其中肺结核268例,肺外结核110例;男204例,女174例,年龄16～ 85岁,平均(48.6±18.2)岁.纳入本院同期体检健康者824名,其中男436名,女388名,年龄16 ～ 80岁,平均(41.6±16.4)岁.所有受试者均进行T-SPOT检测并计算TBAg/PHA比值.本研究另在2017年1-12月纳入广州市胸科医院MTB培养阳性且T-SPOT阳性患者223例作为验证组.本研究为回顾性病例对照研究,采用GraphPad Prism 5.01统计软件进行数据分析,连续变量比较使用Mann-Whitney U检验.结果 378例活动性结核患者中T-SPOT阳性344例,824名健康体检者中T-SPOT阳性204名.以健康体检者为对照组,T-SPOT试验阳性诊断活动性结核的敏感度和特异度分别为91.0％(344/378)和75.2％(620/824).直接利用T-SPOT斑点数结果鉴别活动性结核与MTB潜伏感染的效果不佳,受试者工作特征(ROC)曲线下面积为0.7～0.8.使用TBAg/PHA比值区分活动性结核与MTB潜伏感染的效果明显优于T-SPOT斑点数方法,ROC曲线下面积为0.881(95％CI为0.853 ～ 0.909).当TBAg/PHA＞0.234时,该比值用于区分活动性结核与MTB潜伏感染的敏感度及特异度分别为69.5％(239/344)和94.1％(192/204).TBAg/PHA比值在验证组中用于区分活动性结核与MTB潜伏感染也具有较好效果,ROC曲线下面积为0.901(95％CI为0.872～ 0.931).本研究入组的344例活动性结核患者中96例为肺外结核患者,当TBAg/PHA＞0.234时,TBAg/PHA比值诊断肺外结核的敏感度及特异度分别达到79.2％ (76/96)和94.1％(192/204),ROC曲线下面积为0.932(95％CI为0.897～ 0.967).结论 TBAg/PHA比值在区分活动性结核与MTB潜伏感染的效果优于T-SPOT斑点数的结果,该比值在诊断肺外结核时也具有一定的参考意义.

abstractsObjective The aim of this study was to determine the performance of the ratio of tuberculosis-specific antigen (TBAg) to phytohemagglutinin (PHA) (TBAg/PHA ratio) in T-SPOT assay in the diagnosis of active tuberculosis (ATB).Methods Between January 2014 and January 2017,378 Mycobacterium tuberculosis (MTB) culture positive patients (268 cases of pulmonary tuberculosis,110 extra-pulmonary tuberculosis) and 824 healthy individuals were recruited from Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology.T-SPOT assay was performed and TBAg/PHA ratio was calculated in all the participants.To validate the study,another group of 223 MTB culture positive TB patients with positive T-SPOT results were recruited fron Guangzhou Chest Hospital between January 2017 and December 2017.This was a retrospective case-control study and differences between groups were analyzed using the Mann-Whitney U-test.Results Of the 378 culture positive ATB patients,344 patients had positive T-SPOT results.Of the 824 healthy individuals,204 individuals had positive T-SPOT results.Using healthy individuals as the control group,the sensitivity and specificity of T-SPOT assay in the diagnosis of ATB were 91.0％ (344/378) and 75.2％ (620/824).Directly using T-SPOT results had a limited accuracy in distinguishing ATB from latent tuberculosis infection (LTBI).The area under the receiver operating characteristic (ROC) curve was between 0.7 and 0.8.However,a further calculation of the TBAg/PHA ratio showed a better performance than TBAg in distinguishing these two conditions,and the area under the ROC curve was 0.881 (95％ CI:0.853-0.909).If using the threshold value of 0.234,the sensitivity and specificity of the TBAg/PHA ratio in distinguishing ATB from LTBI were 69.5％ (239/344)and 94.12％ (192/204).The validation data showed that the performance of the TBAg/PHA ratio in distinguishing ATB from LTBI was also satisfactory,and the area under the ROC curve was 0.901 (95％ CI:0.872-0.931).Furthermore,the TBAg/PHA ratio had an important role in the diagnosis of extra-pulmonary tuberculosis.If using the threshold value of 0.234,the sensitivity and specificity of the TBAg/PHA ratio in the diagnosis of extra-pulmonary tuberculosis were 79.2％ (76/96) and 94.1％ (192/204).The area under the ROC curve was 0.932 (95％ CI:0.897-0.967).Conclusions The TBAg/PHA ratio in T-SPOT assay was better than directly using T-SPOT results in distinguishing ATB from LTBI.This ratio also showed a potential use in the diagnosis of extra-pulmonary tuberculosis.