56 2018 1 1431 - [ ]- - T- SPOT.TB 5638 18T-SPOT.TB T-SPOT.TB86.5%(95%CI 71.2%~95.5%) 100%(95%CI 90.5%~100%) 52.9%(95%CI 27.8%~77.0%) 35.3%(95%CI 14.2%~61.7%) 80.0%(95%CI 64.4%~90.9%) 77.1%(95%CI 62.7%~88.0%) 64.3%(95%CI 35.1%~87.2%) 100%(95%CI 54.1%~100%)ROC T-SPOT.TB 47SFC/2.5 10 5 89.2% 88.2%- T-SPOT.TB T-SPOT.TB 47SFC/2.5 10 5 [] - T-SPOT.TB [ ] R521.7 [ ] A [ ] 0577-7402(2018)01-0056-05 [DOI] 10.11855/j.issn.0577-7402.2018.01.11 tuberculous pleurisy ZHOU Min 1, YANG Qing-luan 2, CHEN Hua-xin 1, YU Zhi-ming 1, GAO Liang 1, LIU Qian-qian 2, OU Qin-fang 1* 1 Department of Pulmonary Diseases, Fifth People s Hospital of Wuxi, Wuxi, Jiangsu 214005, China 2 Department of Infectious Diseases, Huashan Hospital affiliated to Fudan University, Shanghai 200040, China * Corresponding author, E-mail: 15211220051@fudan.edu.cn This work was supported by the Project of Science and Technology of Wuxi (CSZ00N1229) [Abstract] Objective To evaluate the diagnostic value of interferon- release assay of blood and pleural effusion for tuberculous pleurisy. Methods Fifty-six adult patients with suspected tuberculous pleurisy were enrolled in our study. The blood and pleural effusion interferon- release assay were measured by T-SPOT.TB test in 38 pleural tuberculosis patients and 18 nontuberculous pleurisy controls. The diagnostic sensitivity, specificity, predictive value of T-SPOT.TB in pleural effusion mononuclear cells (PE-MC) and peripheral mononuclear cells (PBMC) were analyzed. Results The sensitivities and specificities, positive predictive values and negative predictive values, respectively, of the PE-MC and PBMC for diagnosing were as follows: 86.5%(95% confidence interval[ci] 71.2%-95.5%) and 100%(95%CI 90.5%-100%); 52.9%(95%CI 27.8%-77.0%) and 35.3%(95%CI 14.2%- 61.7%); 80.0%(95%CI 64.4%-90.9%) and 77.1%(95%CI 62.7%-88.0%); 64.3%(95%CI 35.1%-87.2%) and 100%(95%CI 54.1%- 100%). By ROC curve analysis, a cut-off value of 47SFC/2.5 10 5 cells in PE-MC showed a sensitivity of 89.2% and a specificity of 88.2%. Conclusion T-SPOT.TB in PE-MC could be an accurate diagnostic method for tuberculous pleurisy in TB endemic settings. Moreover, 47SFC/2.5 10 5 cells might be the optimal cut-off value for diagnosing tuberculous pleurisy. [Key words] interferon- release assay; T-SPOT.TB; pleural effusion; tuberculous pleurisy; diagnosis [ ] (CSZ00N1229) [ ] [ ] 214005 ( ) 200040 ( ) [ ] E-mail 15211220051@fudan.edu.cn [1-2] [3-4] [5]
Med J Chin PLA, Vol. 43, No. 1, January 1, 2018 57 [6] [7] - (IFN- ) [8] T- SPOT.TB IFN- -6(early secretary antigenic target6 ESAT-6) -10(culture filtrate protein10 CFP-10) IFN- T [9] T-SPOT.TB 1 1.1 2014 1 12 2015 6 2016 6 56 ( ) () 1~3 <18 1.2 1.2.1 5ml 50ml 1.2.2IFN- T-SPOT.TB(Oxford Immunotec Abingdon UK) (Mycobacterium tuberculosis)mtb 1(region of difference RD1) T 6h T-SPOT.TB ESAT-6(6 000kD) CFP-10(10 000kD) Ficoll-Hypaque (peripheral blood mononuclear cells PBMCs)(pleural effusion mononuclear cells PE-MCs) PBMCs PE-MCs - ( 2.5 10 5 ) 37 5%CO 2 16~18h ELISPOT (spots forming cells SFC)6 2 PBMCs PE- MCs 10 20 1.2.3 T-SPOT.TB 1.3SPSS 23.0 Mann-Whiney (Fisher's test) P<0.05 2 2.156 3831 51.0(30~72) 4 34 18 1266.9(55~77) 15 (83.3%) 3 (16.7%) (P>0.05) (P=0.03) (P<0.01) ( 1) 2.2T-SPOT.TB 38 37 T-SPOT.TB 32 86.5% 37 T- SPOT.TB 100% 18 17 T- SPOT.TB 8 47.1% 17 T-SPOT.TB11 64.7% T-SPOT.TB(P<0.05 1) T- SPOT.TB ESAT-6 CFP-10 1 6SFC/2.5 10 5 T- SPOT.TB 86.5%(95%CI 71.2%~95.5%) 100%(95%CI 90.5%~100%) 52.9%(95%CI 27.8%~77.0%) 35.3%(95%CI 14.2%~61.7%) 80.0%(95%CI 64.4%~90.9%) 77.1%(95%CI 62.7%~88.0%) 64.3%(95%CI 35.1%~87.2%) 100%(95%CI
58 2018 1 1431 1 56 Tab.1 Comparison of various diagnostic index in 56 patients with suspected tuberculous pleurisy Item Tuberculous pleurisy (n=38) Non-tuberculous pleurisy (n=18) P value T-SPOT.TB [n(%)] PBMCs T-SPOT.TB 32/37(86.5) 8/17(47.1) 0.0056 PE-MCs T-SPOT.TB 37/37(100) 11/17(64.7) 0.0005 Blood [median (IQR)] WBC (10 9 /L) 5.57(4.49-6.68) 6.61(4.85-9.16) 0.0559 Neutrophil (%) 68.50(58.35-73.53) 71.25(65.50-75.30) 0.1886 Lymphocyte (%) 22.50(16.73-27.03) 19.00(15.50-24.60) 0.3309 Hb (g/l) 121.50(108.80-133.80) 124.00(111.30-141.30) 0.5000 PLT (10 9 /L) 263.50(173.80-341.00) 193.50(155.00-244.00) 0.0880 ESR (mm/h) 57.50(42.25-75.25) 38.00(22.50-68.50) 0.2168 CSF [median (IQR)] Protein (g/l) 40.95(40.0-45.45) 46.00(34.73-48.50) 0.5435 Lymphocyte (%) 84.00(72.98-88.93) 75.00(32.25-84.75) 0.0363 ADA (U/L) 42.60(14.85-59.70) 12.00(7.0-17.0) 0.0003 LDH (U/L) 383.00(221.10-616.10) 387.00(167.00-557.00) 0.9809 PBMCs. Peripheral blood mononuclear cells; PE-MCs. Pleural effusion mononuclear cells; WBC. White blood cell; Hb. Hemoglobin; PLT. Platelet; ESR. Erythrocyte sedimentation rate; ADA. Adenosine deaminase; LDH. Lactic dehydrogenase; IQR. Interquartile range IFN- producting T cell responses (SFC/2.5 10 5 cells) 600 500 400 300 200 150 100 50 0 1 IFN-ESAT-6 CFP-10 Fig.1 Box-and-whisker plot showing responses to ESAT-6 and CFP-10 according to the PBMC and PE-MC T-SPOY.TB PBMCs. Peripheral blood mononuclear cells; PE-MCs. Pleural effusion mononuclear cells; TB. Tuberculous pleurisy; non-tb. Nontuberculous pleurisy; A. ESAT-6; B. CFP-10; P<0.05 A B A B A B A B TB non-tb TB non-tb PBMCs PE-MCs 54.1%~100% 2) T- SPOT.TB 2.3 ROCT- SPOT.TB ROC 58 T- SPOT.TB T- SPOT.TB ROC (AUC) 0.9459(95%CI 0.891~1.000 P<0.001) T-SPOT.TB AUC(0.7663 95%CI 0.666~0.860 P <0.001 2)ROC T- SPOT.TB 47SFC/2.5 10 5 89.2% 88.2% 94.3% 78.9% 7.58 0.123 T-SPOT.TB 97.4% 90.9% 0.047 2T-SPOT.TB (%) Tab.2 Diagnostic performance of PBMC and PE-MC T-SPOT.TB in the study population (%) T-SPOT.TB Sensitivity Specificity PPV NPV LR + LR PBMCs>6SFC 1 86.5(71.2-95.5) 52.9(27.8-77.0) 80.0(64.4-90.9) 64.3(35.1-87.2) 1.84(1.09-3.09) 0.255(0.101-0.647) PE-MCs>6SFC 100.0(90.5-100.0) 35.3(14.2-61.7) 77.1(62.7-88) 100.0(54.1-100.0) 1.55(1.09-2.2) PE-MCs>47SFC 2 89.2(74.6-97.0) 88.2(63.6-98.5) 94.3(80.8-99.3) 78.9(54.4-93.9) 7.58(2.05-28) 0.123(0.048-0.314) PBMCs>6SFC or PE-MCs>6SFC 100.0(90.5-100.0) 29.4(10.3-56.0) 75.5(61.1-86.7) 100.0(47.8-100.0) 1.42(1.04-1.93) PBMCs>6SFC or PE-MCs>47SFC 97.4(86.2-99.9) 55.6(30.8-78.5) 82.2(67.9-92) 90.9(58.7-99.8) 2.19(1.3-3.68) 0.047(0.007-0.342) PBMCs>6SFC and PE-MCs>6SFC 86.1(70.5-95.3) 56.3(29.9-80.2) 81.6(65.7-92.3) 64.3(35.1-87.2) 1.97(1.11-3.48) 0.247(0.0983-0.62) PBMCs>6SFC and PE-MCs>47SFC 73.7(56.9-86.6) 88.9(65.3-98.6) 93.3(77.9-99.2) 61.5(40.6-79.8) 6.63(1.77-24.8) 0.296(0.170-0.516) PBMCs. Peripheral blood mononuclear cells; PE-MCs. Pleural effusion mononuclear cells; SFC. Spots forming cells; PPV. Positive predictive value; NPV. Negative predictive value; LR +. Positive likelihood ratio; LR. Negative likelihood ratio. 1 SFC is short for SFCs /2.5 10 5 mononuclear cells; 2 Cut-off derived from the area under the curve by the Youden index
Med J Chin PLA, Vol. 43, No. 1, January 1, 2018 59 Sensitivity 0 0 0.5 1.0 1-specificity 2T-SPOT.TBROC Fig.2 ROC curves in PBMCs and PE-MCs T-SPOT.TB for diagnosis of tuberculous pleurisy ( 2) 3 1.0 0.5 PBMC (0.7663) PE-MC (0.9459) T-SPOT.TB T-SPOT.TB T-SPOT.TB 6SFC/2.5 10 5 IFN- MtbT T T Souza [10] T Barnes [11] CD4 + T T IFN- IFN- T-SPOT.TBT-SPOT.TB IFN- 93% [12] 6SFC/2.5 10 5 T-SPOT.TB T-SPOT.TB 47SFC/2.5 10 5 86.5%89.2% 52.9%88.2% 80.0%94.3% 64.3%78.9%1.847.58 0.2550.123 T- SPOT.TB 6SFC/2.5 10 5 T- SPOT.TB [9] 187 T- SPOT.TB T- SPOT.TB 6SFC/2.5 10 5 T-SPOT.TB ROC T- SPOT.TB AUC 0.9459T- SPOT. TB(0.7663) T-SPOT.TB 47SFC/2.5 10 5 T-SPOT.TB 89.2% 88.2% Zhang [13] 98 T-SPOT.TB (94.5%) (76.1%) 54 SFC/2.5 10 5 4 T-SPOT.TB IFN- T-SPOT.TB T-SPOT.TB 47SFC/2.5 10 5 T-SPOT.TB [1] Hooper CE, Lee YC, Maskell NA. Interferon-gamma release assays for the diagnosis of TB pleural effusions: hype or real hope?[ J]. Curr Opin Pulm Med, 2009, 15(4): 358-365. [2] Shi XP, Wang J, Wang X, et al. Clinical application of T-spot test of Mycobacterium tuberculosis infection for diagnosis of suspected pulmonary tuberculosis patients[ J]. Med J Chin PLA, 2017, 42(11): 996-1000. [,,,. T [ J]., 2017, 42(11): 996-1000.] [3] Porcel JM. Tuberculous pleural effusion[ J]. Lung, 2009, 187(5): 263-270. [4] Liu HM, Chu Z, Tian R, et al. Application of IL-10 and IL-12 detection in differential diagnosis of tuberculous and malignant pleural effusion[ J]. J Jilin Univ (Med Ed), 2017, 43(4): 782-786, 861. [,,,. IL-10 IL-12 [ J]. ( ), 2017, 43(4): 782-786, 861.] [5] Greco S, Girardi E, Masciangelo R, et al. Adenosine deaminase and interferon gamma measurement for the diagnosis of tuberculous pleurisy: a meta-analysis[ J]. Int J Tuberc Lung Dis,
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