Factors associated with differential T cell responses to antigens ESAT-6 and CFP-10 in pulmonary tuberculosis patients

The T-SPOT.TB assay detects cellular immune responses to 2 core Mycobacterium tuberculosis antigens, early secreted antigenic target of 6-kDa protein (ESAT-6) and culture filtrate protein-10 (CFP-10). T-SPOT.TB has been recently used for auxiliary diagnosis of active pulmonary tuberculosis (PTB). However, testing can produce inconsistent results due to differential PTB patient immune responses to these antigens, prompting us to identify factors underlying inconsistent results.Data were retrospectively analyzed from 1225 confirmed PTB patients who underwent T-SPOT.TB testing at 5 specialized tuberculosis hospitals in China between December 2012 and November 2015. Numbers of spot-forming cells (SFCs) reflecting T cell responses to ESAT-6 and CFP-10 antigens were recorded then analyzed via multivariable logistic regression to reveal factors underlying discordant T cell responses to these antigens.The agreement rate of 84.98% (82.85%–86.94%) between PTB patient ESAT-6 and CFP-10 responses demonstrated high concordance. Additionally, positivity rates were higher for ESAT-6 than for CFP-10 (84.8% vs 80.7%, P < .001), with ESAT-6 and CFP-10 microwell SFC numbers for each single positive group not differing significantly (P > .99), while spot numbers of the single positive group were lower than numbers for the double positive group (P < .001). Elderly patients (aged ≥66 years) and patients receiving retreatment were most likely to have discordance results.ESAT-6 promoted significantly more positive T-SPOT.TB results than did CFP-10 in PTB patients. Advanced age and retreatment status were correlated with discordant ESAT-6 and CFP-10 results. Assessment of factors underlying discordance may lead to improved PTB diagnosis using T-SPOT.TB.     

Diagnóstico de la infección tuberculosa en pacientes inmunodeprimidos y/o candidatos a terapias biológicas mediante el uso combinado de dos pruebas IGRA: T-SPOT.TB/QuantiFERON TB Gold In-Tube vs. T-SPOT.TB/QuantiFERON TB Gold Plus

IntroductionThe diagnosis of latent tuberculous infection (LTI) by IGRA continues to generate debate. Experience in the simultaneous use of 2 IGRA tests is scant. The aim of this study was to compare the results of 2 versions of QuantiFERON-TB Gold (In-Tube/Plus) with those of T-SPOT.TB, and to analyse the effectiveness of a dual strategy (T-SPOT.TB + QTF) for the diagnosis of LTI in an immunosuppressed population.MethodsWe conducted a prospective study (May 2015-June 2017) that included 2,999 immunosuppressed patients and/or candidates for biologics, in whom 2 simultaneous IGRA tests were performed: Group 1 (1535 patients): T-SPOT.TB + QuantiFERON-TB Gold-In-Tube (QTF-GIT); Group 2 (1464 patients): T-SPOT.TB + QuantiFERON-TB Gold Plus (QTF-Plus).ResultsThe concordance between QTF-GIT and T-SPOT.TB was 83.19% (κ=0.532). The percentage of positive, negative, and indeterminate results were, respectively: 14.33% vs. 17.06%; 82.41% vs. 74.46%; and 3.25% vs. 8.46%. The concordance between QTF-Plus and T-SPOT.TB was 87.56% (κ=0.609). The percentage of positive, negative, and indeterminate results were, respectively: 15.02% vs. 15.36%; 82.92% vs. 79.37%; and 2.04% vs. 5.25%. Discrepancies between T-SPOT.TB and QTF-Plus were 12.43%, suggesting that 103 patients were positive and another 79 were negative due exclusively to 1 of the 2 IGRAs.ConclusionsGreater concordance was found between QTF-Plus and T-SPOT.TB than between QTF-GIT and T-SPOT.TB. However, we believe that the proportion of discrepancies between T-SPOT.TB and QTF-Plus is sufficiently important from a clinical point of view to justify the simultaneous use of 2 IGRA in this specific patient group.     

结核感染T细胞斑点试验对结核性胸膜炎的诊断价值

目的：评价结核感染T细胞斑点试验（T-SPOT.TB）对诊断结核性胸膜炎的价值。方法前瞻性纳入疑诊结核性胸膜炎患者100例,进行外周血T-SPOT.TB、血清结核抗体、胸腔积液腺苷脱氨酶（ADA）检测,并比较外周血T-SPOT.TB、胸腔积液ADA、血清结核抗体检测诊断结核性胸膜炎的灵敏度。外周血T-SPOT.TB、胸腔积液ADA、血清结核抗体检测诊断结核性胸膜炎的灵敏度分别为92.6%、95.5%、36.4%;特异度分别为92.3%、75%、76.8%;阳性预测值分别为96.2%、91.7%、57.1%,阴性预测值分别为85.7%、85.7%、35.5%。T-SPOT.TB特异度与后两种方法比较,差异均有统计学意义（均P<0.05）。灵敏度及阳性预测值、阴性预测值与胸水ADA比较,差异均无统计学意义;与血清结核抗体比较,差异均有统计学意义（均P<0.05）。结论 T-SPOT.TB对诊断结核性胸膜炎有较高的灵敏度及特异度,对临床应用有重要的参考价值。     

结核感染T细胞斑点试验在手、腕部腱鞘结核诊断中的应用评价

=O4 探讨结核感染T细胞斑点试验(T-cell spot of Tuberculosis,T-SPOT.TB)在手、腕部腱鞘结核诊断中的临床应用价值。方法通过对2012年1月至2018年1月我院收集 64例怀疑手、腕部腱鞘结核临床资料进行回顾性分析,根据病理诊断及临床表现判断有无结核分枝杆菌感染;全部病例均经过T-SPOT.TB和胶体金标法分别进行体外γ-干扰素释放试验和血清结核抗体检测,采用Kappa、χ²检验进行统计学分析。-结果- 共收集分析相关病例64例,其中诊断为手、腕部腱鞘结核(结核病例)21例,非手、腕部腱鞘结核(非结核病例)43例。经T-SPOT.TB检测,结核病例阳性者20例,非结核病例阴性者40例,灵敏度为95.2%,特异度为93.0%,阳性预测值为87.6%,阴性预测值为97.6%。经胶体金标法检测血清结核抗体,结核病例阳性者5例,非结核病例阴性者37例,灵敏度为23.8%,特异度为86.0%,阳性预测值为45.4%,阴性预测值为69.8%。与临床诊断比较,T-SPOT.TB和胶体金标法的Kappa值分别为0.862和0.112,T-SPOT.TB比胶体金标法具有更好的一致性,且灵敏度、阳性预测值和阴性预测值均明显更高,差异有统计学意义(P<0.05)。-结论- T-SPOT.TB在手、腕部腱鞘结核诊断中具有良好的辅助诊断价值。     

T-SPOT.TB在涂阴肺结核中的快速诊断价值

目的评价结核感染T细胞试验(T-SPOT.TB)在涂阴肺结核病诊断上的价值。方法利用T-SPOT.TB、TBDNA、TB-DOT 3种结核病诊断方法对112例确诊涂阴肺结核病患者和60例非结核病对照者分别进行检测。结果 T-SPOT.TB试验检测灵敏度为88.3%,TB-DNA、TB-DOT的灵敏度依次为25.9%、58.9%,与T-SPOT.TB试验相比,差异均有统计学意义(χ2=86.6,P0.05;χ2=23.3,P0.05);T-SPOT.TB试验特异度为96.7%,显著高于TB-DOT(78.3%),差异有统计学意义(χ~2=9.22,P0.05)。结论 T-SPOT.TB对涂阴肺结核病的敏感性和特异性都有明显的优势,可以作为涂阴肺结核病早期诊断的一种辅助检查手段,具快速准确的诊断价值。     

外周血结核感染T细胞斑点试验在结核病中的应用价值研究

目的 探讨外周血结核感染T细胞斑点试验（T-SPOT.TB）在结核病中的应用价值。方法 回顾行T-SPOT.TB检查的住院疑似结核病患者536例;根据患者诊断分为结核病组和非结核病组;根据活动性、病变部位和化疗史将结核病患者分为活动性结核组和非活动性结核组,肺结核组、肺外结核病组和混合组,初治结核组和复治结核组。比较上述各组间T-SPOT.TB诊断价值以及分析肺外结核组各种结核病阳性率。结果536例患者中有344例确诊为结核病,其中T-SPOT.TB试验阳性296例,阴性48例,灵敏度为86.0%（296/344）;192例非结核病患者中,T-SPOT.TB阴性162例,特异度为84.4%（162/192）。非活动性结核组和活动性结核组阳性率分别为44.4%和88.4%（P＜0.01）。肺结核组、肺外结核病组和混合组阳性率分别为87.3%、70.4%和94.3%（P＜0.01）;初治结核组和复治结核组阳性率分别为87.1%和100%（P＜0.05）。肺外结核以结核性脑膜炎、胸膜炎和腹膜炎最常见,结核性脑膜炎阳性率最低为42.9%。结论外周血T-SPOT.TB试验在诊断住院患者结核病中具有很高的灵敏度和特异度;活动性结核和复治结核敏感度高于非活动性结核和初治结核;结核性脑膜炎敏感度不高,而在其它肺外结核具有较高临床应用价值。     

γ-干扰素释放分析T-SPOT.TB在结核性疾病中的诊断价值

目的评价γ-干扰素释放分析T-SPOT.TB检测在结核性疾病中的诊断价值。方法采用T-SPOT.TB试剂盒对疑诊或待排结核患者外周血中释放γ-干扰素的结核分枝杆菌特异性T淋巴细胞进行检测。结果γ-干扰素释放分析T-SPOT.TB检测在结核性疾病阳性检出率为83.3%(20/24),明显高于结核菌素试验(tuberculin skin test,TST)的41.7%(10/24)、涂片找抗酸杆菌的26.7%(4/15)、分枝杆菌分离培养的22.2%(2/9),差异有统计学意义(P<0.05)。γ-干扰素释放分析T-SPOT.TB检测诊断结核性疾病敏感性、特异性分别为83.3%、96.4%,显著优于结核菌素试验。结论γ-干扰素释放分析T-SPOT.TB检测是诊断结核的快速敏感方法,在结核性疾病诊断中有重要价值。     

结核感染T细胞斑点试验在骨与关节结核诊断中的价值

目的探讨结核感染T细胞斑点试验(T-SPOT TB)在临床诊断骨与关节结核的应用价值。方法收集154例疑似骨与关节结核患者外周抗凝血标本,依据细菌学检验、病理学结果及临床表现判定有无结核分枝杆菌感染;其中确诊骨与关节结核73例,非结核感染81例,分别进行T-SPOT TB和结核抗体(TB-Ab)检测,并分析T-SPOT TB在骨与关节结核诊断中的敏感度和特异度。结果 73例确诊骨与关节结核中,64例T-SPOT TB阳性;81例非结核中,72例T-SPOT TB阴性;T-SPOT TB检测敏感度为87.67%(64/73),TB-Ab为41.10%(30/73),T-SPOT TB诊断骨与关节结核的敏感度显著高于TB-Ab(P0.001);T-SPOT TB检测特异度为88.89%(72/81),TB-Ab为71.60%(58/81),T-SPOT TB特异度也高于TB-Ab(P=0.006)。在结核组中,涂阳与涂阴两组T-SPOT TB阳性检出率分别为95.45%(21/22)及86.49%(32/37),差异无统计学意义(P0.05)。在结核组中,病理诊断阳性率92.16%(47/51)与T-SPOT TB总阳性率87.67%(64/73)比较差异无统计学意义(P0.05)。结论 T-SPOT TB在诊断骨与关节结核中具有良好的敏感度和特异度,具有重要临床应用价值。     

Xpert MTB/RIF和T-SPOT.TB对涂阴肺结核诊断价值的评估

目的评估并比较Xpert MTB/RIF和T-SPOT.TB对涂阴肺结核的诊断价值。方法收集2014年12月至2015年12月天津市海河医院门诊和住院的呼吸疾病患者208例,分为结核组125例和对照组83例,同时对其痰液样本行涂片镜检、液体快速培养和Xpert MTB/RIF检测,对其血液样本行T-SPOT.TB试验。结果 Xpert MTB/RIF诊断涂阴肺结核的敏感性、特异性、ROC曲线下面积(AUC)及优势比(odds ratio,OR)分别为56.5%(95%CI:45.8%~66.8%)、98.8%(95%CI:93.5%~100.0%)、0.777(95%CI:0.708~0.836)及106.60(χ~2=62.87,P0.01);T-SPOT.TB诊断涂阴肺结核的敏感性、特异性、AUC及OR值分别为83.7%(95%CI:74.5%~90.5%)、62.7%(95%CI:51.3%~73.0%)、0.732(95%CI:0.660~0.796)及8.61(χ~2=39.44,P0.01);两者敏感性(χ~2=18.58)和特异性(χ~2=28.03)的差异有统计学意义(P0.05),AUC的差异无统计学意义(Z=1.235,P0.05);Xpert MTB/RIF阴性的涂阴肺结核患者T-SPOT.TB阳性率为70.0%。结论 Xpert MTB/RIF和T-SPOT.TB均有助于早期、快速、准确地辅助诊断肺结核,T-SPOT.TB可以作为Xpert MTB/RIF的后续试验辅助诊断Xpert MTB/RIF阴性的涂阴肺结核。