T-SPOT.TB在肺结核病诊断中应用价值的探讨
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摘要
研究背景及目的：
结核病是由结核分枝杆菌(Mycobacterium tuberculosis,MTB,简称结核杆菌或结核菌)引起的慢性感染性疾病。近年来，随着人体免疫缺陷病毒(Human ImmunodeficiencyViruses，HIV)感染、艾滋病的流行，流动性人口增多、移民增加，以及结核菌耐药性的加重，导致了结核病的发病率逐年呈上升趋势。目前全球有超过1/3（约20亿）人口感染了MTB，其中活动性肺结核患者达2000万，每年超过800万新发结核病患者，死于结核感染的人数达到300万，而我国更是位列结核病高负担国家的第二位，全国现有5.5亿人口感染结核，其中活动性肺结核患者450万，死亡人数每年超过13万。严峻的结核病态势促使结核病的诊断和治疗再度引起人们的关注，而相对于传统的结核感染诊断技术敏感性及特异性较差，近年来一种以结核抗原特异性T细胞反应为基础的新的结核病诊断方法即T-SPOT.TB逐步建立与开展起来。本研究将探讨在高感染背景下T-SPOT.TB在活动性结核病诊断中的应用价值。
方法：
前瞻性纳入吉林大学第二医院2011年9月至2012年3月收治住院患者中因发热、肺部阴影、胸腔积液等原因入院，需排除结核感染的患者90例进行外周血T-SPOT.TB检测，将其T-SPOT.TB检测结果与最终临床诊断进行比较，以敏感性、特异性、阳性预测值、阴性预测值、阳性似然比、阴性似然比为评价指标。并在确诊结核病患者中，比较分析T-SPOT.TB、痰抗酸染色涂片镜检、血清结核抗体、纤支镜病理检查诊断及T-SPOT.TB联合纤支镜病理检查的阳性率。
结果：
本实验中T-SPOT.TB敏感性为86.4％（19/22），特异性为72.1％（44/61），T-SPOT.TB阴性预测值93.6％，阳性预测值为52.8％，阴性似然比0.19，阳性似然比2.89。52例非浆膜腔积液患者中，T-SPOT.TB敏感性为91.7％（11/12），特异性为85％（34/40），阴性预测值97.1％，阳性预测值为64.7％，阴性似然比0.10，阳性似然比6.11；31例浆膜腔积液患者中，T-SPOT.TB敏感性为80％（8/10），特异性为48％（10/21），阴性预测值83.3％，阳性预测值为42.1％，阴性似然比0.42，阳性似然比1.54。确诊结核病组患者T-SPOT.TB试验、血清结核抗体、痰或纤支镜痰/灌洗液抗酸染色涂片、支气管镜组织病理试验敏感性分别是86.4%、22.2%、9.1%、57.1%。T-SPOT.TB试验联合纤维支气管镜病理检查敏感性为100%。结论：
T-SPOT.TB阴性结果有助于排除活动性结核病的诊断。T-SPOT.TB试验联合纤维支气管镜病理检查对活动性结核感染诊断有较大的应用价值。
Backgroud and objective：Tuberculosis is a kind of infectious bacterial disease causedby Mycobacterium tuberculosis．In recently years，incidence of tuberculosis has risedbecause of increasing incidences of HIV infection，international immigration and drugresistance MTB．To now，about2billion people have infected with MTB worldwide，20million patients have active pulmonary tuberculosis，and there are8million new patientswith tuberculosis yearly．Annually，3million patients (0.13million chineses) died of TB．InChina, among550milion patients infected with MTB，4.5milion patients have activepulmonary tuberculosis, which has caused high-burden．This severe condition urged us topay attention to the diagnosis and treatment of TB．But traditional diagnostic methods for TBhave lower sensitivity and worser specificity．In recent years, T-SPOT.TB was found anddeveloped gradually, which is a kind of new diagnostic methods for TB and based onthe response of MTB antigen-specific T cells．In this study, we discussed application ofT-SPOT.TB in the diagnosis of TB.
Methods：We designed a prospective study enrolling90patients with suspected TB,who were admitted in The Second Hospital of Jilin University from September2011toMarch2012．We assessed the value of peripheral blood T-SPOT.TB assay for the diagnosisof active tuberculosis with comparing T-SPOT.TB test results and final clinical diagnosis inroutine clinical practice. To evaluate the application of T.SPOT-TB in the diagnosis ofpulmonary tuberculosis by detecting IFN-gamma-secreting T cells, we analyzed sensitivity、specificity、positive predictive value、negative predictive value、positive likelihood ratio、negative likelihood ratio of T.SPOT-TB．Among patients who diagnosed tuberculosis，wecompared the positive rate of T-SPOT.TB assay，acid-fast staining of sputamentum，tuberculosis antibody with ELISA assay，hisopathology diagnosis，and combination ofT-SPOT.TB assay and hisopathology diagnosis.
Results：Among all90patients, sensitivity of T-SPOT.TB assay for active tuberculosiswas86.4％(19/22)， specificity was72.1％(44/61)，negative predictive value was93.6％， positive predictive value was52.8％，negative likelihood ratio was0.19，and positivelikelihood ratio was2.89．In52patients with non-serous cavity effusion，sensitivity ofT-SPOT.TB was91.7％(11/12)，specificity was85％(34/40)，negative predictive value was97.1％，positive predictive value was64.7％，negative likelihood ratio was0.10，andpositive likelihood ratio was6.11；In31patients with cavity effusion, sensitivity ofT-SPOT.TB was80％(8/10)，specificity was48％(10/21)，negative predictive value was83.3％，positive predictive value was42.1％，negative likelihood ratio was0.42，and positivelikelihood ratio was1.54.
Among22patients diagnosed active tuberculosis，the positive rate of T-SPOT.TBassay，acid-fast staining of sputamentum，tuberculosis antibody with ELISA assay andhisopathology diagnosis were86.3%、22.2%、9.1%、57.1%respectively. Sensitivity ofcombination of T-SPOT.TB assay and hisopathology diagnosis was100%.Conclusion：
The negative result of T-SPOT.TB is useful to exclude active tuberculosis. Combinationof T-SPOT.TB assay and hisopathology diagnosis is recommended in routine clinicalpractice．
结核病是由结核分枝杆菌(Mycobacterium tuberculosis,MTB,简称结核杆菌或结核菌)引起的慢性感染性疾病。近年来，随着人体免疫缺陷病毒(Human ImmunodeficiencyViruses，HIV)感染、艾滋病的流行，流动性人口增多、移民增加，以及结核菌耐药性的加重，导致了结核病的发病率逐年呈上升趋势。目前全球有超过1/3（约20亿）人口感染了MTB，其中活动性肺结核患者达2000万，每年超过800万新发结核病患者，死于结核感染的人数达到300万，而我国更是位列结核病高负担国家的第二位，全国现有5.5亿人口感染结核，其中活动性肺结核患者450万，死亡人数每年超过13万。严峻的结核病态势促使结核病的诊断和治疗再度引起人们的关注，而相对于传统的结核感染诊断技术敏感性及特异性较差，近年来一种以结核抗原特异性T细胞反应为基础的新的结核病诊断方法即T-SPOT.TB逐步建立与开展起来。本研究将探讨在高感染背景下T-SPOT.TB在活动性结核病诊断中的应用价值。
方法：
前瞻性纳入吉林大学第二医院2011年9月至2012年3月收治住院患者中因发热、肺部阴影、胸腔积液等原因入院，需排除结核感染的患者90例进行外周血T-SPOT.TB检测，将其T-SPOT.TB检测结果与最终临床诊断进行比较，以敏感性、特异性、阳性预测值、阴性预测值、阳性似然比、阴性似然比为评价指标。并在确诊结核病患者中，比较分析T-SPOT.TB、痰抗酸染色涂片镜检、血清结核抗体、纤支镜病理检查诊断及T-SPOT.TB联合纤支镜病理检查的阳性率。
结果：
本实验中T-SPOT.TB敏感性为86.4％（19/22），特异性为72.1％（44/61），T-SPOT.TB阴性预测值93.6％，阳性预测值为52.8％，阴性似然比0.19，阳性似然比2.89。52例非浆膜腔积液患者中，T-SPOT.TB敏感性为91.7％（11/12），特异性为85％（34/40），阴性预测值97.1％，阳性预测值为64.7％，阴性似然比0.10，阳性似然比6.11；31例浆膜腔积液患者中，T-SPOT.TB敏感性为80％（8/10），特异性为48％（10/21），阴性预测值83.3％，阳性预测值为42.1％，阴性似然比0.42，阳性似然比1.54。确诊结核病组患者T-SPOT.TB试验、血清结核抗体、痰或纤支镜痰/灌洗液抗酸染色涂片、支气管镜组织病理试验敏感性分别是86.4%、22.2%、9.1%、57.1%。T-SPOT.TB试验联合纤维支气管镜病理检查敏感性为100%。结论：
T-SPOT.TB阴性结果有助于排除活动性结核病的诊断。T-SPOT.TB试验联合纤维支气管镜病理检查对活动性结核感染诊断有较大的应用价值。
Backgroud and objective：Tuberculosis is a kind of infectious bacterial disease causedby Mycobacterium tuberculosis．In recently years，incidence of tuberculosis has risedbecause of increasing incidences of HIV infection，international immigration and drugresistance MTB．To now，about2billion people have infected with MTB worldwide，20million patients have active pulmonary tuberculosis，and there are8million new patientswith tuberculosis yearly．Annually，3million patients (0.13million chineses) died of TB．InChina, among550milion patients infected with MTB，4.5milion patients have activepulmonary tuberculosis, which has caused high-burden．This severe condition urged us topay attention to the diagnosis and treatment of TB．But traditional diagnostic methods for TBhave lower sensitivity and worser specificity．In recent years, T-SPOT.TB was found anddeveloped gradually, which is a kind of new diagnostic methods for TB and based onthe response of MTB antigen-specific T cells．In this study, we discussed application ofT-SPOT.TB in the diagnosis of TB.
Methods：We designed a prospective study enrolling90patients with suspected TB,who were admitted in The Second Hospital of Jilin University from September2011toMarch2012．We assessed the value of peripheral blood T-SPOT.TB assay for the diagnosisof active tuberculosis with comparing T-SPOT.TB test results and final clinical diagnosis inroutine clinical practice. To evaluate the application of T.SPOT-TB in the diagnosis ofpulmonary tuberculosis by detecting IFN-gamma-secreting T cells, we analyzed sensitivity、specificity、positive predictive value、negative predictive value、positive likelihood ratio、negative likelihood ratio of T.SPOT-TB．Among patients who diagnosed tuberculosis，wecompared the positive rate of T-SPOT.TB assay，acid-fast staining of sputamentum，tuberculosis antibody with ELISA assay，hisopathology diagnosis，and combination ofT-SPOT.TB assay and hisopathology diagnosis.
Results：Among all90patients, sensitivity of T-SPOT.TB assay for active tuberculosiswas86.4％(19/22)， specificity was72.1％(44/61)，negative predictive value was93.6％， positive predictive value was52.8％，negative likelihood ratio was0.19，and positivelikelihood ratio was2.89．In52patients with non-serous cavity effusion，sensitivity ofT-SPOT.TB was91.7％(11/12)，specificity was85％(34/40)，negative predictive value was97.1％，positive predictive value was64.7％，negative likelihood ratio was0.10，andpositive likelihood ratio was6.11；In31patients with cavity effusion, sensitivity ofT-SPOT.TB was80％(8/10)，specificity was48％(10/21)，negative predictive value was83.3％，positive predictive value was42.1％，negative likelihood ratio was0.42，and positivelikelihood ratio was1.54.
Among22patients diagnosed active tuberculosis，the positive rate of T-SPOT.TBassay，acid-fast staining of sputamentum，tuberculosis antibody with ELISA assay andhisopathology diagnosis were86.3%、22.2%、9.1%、57.1%respectively. Sensitivity ofcombination of T-SPOT.TB assay and hisopathology diagnosis was100%.Conclusion：
The negative result of T-SPOT.TB is useful to exclude active tuberculosis. Combinationof T-SPOT.TB assay and hisopathology diagnosis is recommended in routine clinicalpractice．
引文
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[23]张舒，邵凌云，等.应用T细胞酶联免疫斑点法诊断人类免疫缺陷病毒感染合并结核潜伏感染的实验研究[J].微生物与感染，2007，2（3），132-137.