{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T01:19:41Z","timestamp":1778635181410,"version":"3.51.4"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,1,4]],"date-time":"2021-01-04T00:00:00Z","timestamp":1609718400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,1,4]],"date-time":"2021-01-04T00:00:00Z","timestamp":1609718400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009601","name":"Beijing Municipal Administration of Hospitals","doi-asserted-by":"publisher","award":["DFL20151501"],"award-info":[{"award-number":["DFL20151501"]}],"id":[{"id":"10.13039\/501100009601","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Key Project of the Department of Science and Technology, Beijing, China","award":["D141107005214003"],"award-info":[{"award-number":["D141107005214003"]}]},{"name":"Key Project of the Department of Science and Technology, Beijing, China","award":["D181100000418003"],"award-info":[{"award-number":["D181100000418003"]}]},{"name":"Key Project of the Department of Science and Technology, Beijing, China","award":["Z191100006619078"],"award-info":[{"award-number":["Z191100006619078"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Infect Dis"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Tuberculous pleural effusion (TPE) is the most common extrapulmonary manifestation and may have lasting effect on lung function. However conventional diagnostic tests for TPE register multiple limitations. This study estimates diagnostic efficacy of the interferon gamma release assay (IGRA: T-SPOT.TB) in TPE patients of different characteristics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed a prospective, single-centre study including all suspected pleural effusion patients consecutively enrolled from June 2015 to October 2018. Through receiver operating characteristic (ROC) curves, technical cut-offs and the utility of T-SPOT on pleural fluid (PF) were determined and analysed. Logistic regression analysis was performed to obtain the independent risk factors for TPE, and evaluated the performance of the T-SPOT assay stratified by risk factors in comparison to ADA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 601 individuals were consecutively recruited. The maximum spot-forming cells (SFCs) of early secretory antigenic target-6 (ESAT-6) and culture filtrate protein-10 (CFP-10) in the PF T-SPOT assay had the best diagnostic efficiency in our study, which was equal to ADA (0.885 vs 0.887,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.957) and superior to peripheral blood (PB), with a sensitivity of 83.0% and a specificity of 83.1% (The cut-off value was 466 SFCs\/10\n                      <jats:sup>6<\/jats:sup>\n                      mononuclear cells). Among the TPE patients with low ADA (&lt;\u200940\u2009IU\/L), the sensitivity and specificity of PF T-SPOT were still 87.9 and 90.5%, respectively. The utility of ADA was negatively related to increasing age, but the PF T-SPOT test had a steady performance at all ages. Age (&lt;\u200945\u2009yrs.; odds ratio (OR)\u2009=\u20095.61, 95% confidence interval (CI) 3.59\u20138.78;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.001), gender (male; OR\u2009=\u20092.68, 95% CI 1.75\u20132.88;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.001) and body mass index (BMI) (&lt;\u200922; OR\u2009=\u20091.93, 95% CI 1.30\u20132.88;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.001) were independently associated with the risk of TB by multivariate logistic regression analysis. Notably, when stratified by risk factor, the sensitivity of PF T-SPOT was superior to the sensitivity for ADA (76.5% vs. 23.5%,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.016) and had noninferior specificity (84.4% vs. 96.9%,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.370).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In conclusion, the PF T-SPOT assay can effectively discriminate TPE patients whose ADA is lower than 40\u2009IU\/L and is superior to ADA in unconventional TPE patients (age\u2009\u2265\u200945\u2009yrs., female or BMI\u2009\u2265\u200922). The PF T-SPOT assay is an excellent choice to supplement ADA to diagnose TPE.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12879-020-05676-2","type":"journal-article","created":{"date-parts":[[2021,1,4]],"date-time":"2021-01-04T10:04:07Z","timestamp":1609754647000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Use of T-SPOT.TB for the diagnosis of unconventional pleural tuberculosis is superior to ADA in high prevalence areas: a\u00a0prospective analysis of 601 cases"],"prefix":"10.1186","volume":"21","author":[{"given":"Xinting","family":"Yang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingtao","family":"Liang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liping","family":"Pan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongfei","family":"Duan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hua","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongyan","family":"Jia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Boping","family":"Du","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rongrong","family":"Wei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aiying","family":"Xing","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zongde","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyou","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,1,4]]},"reference":[{"key":"5676_CR1","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1164\/rccm.2111019","volume":"167","author":"MB Conde","year":"2003","unstructured":"Conde MB, Loivos AC, Rezende VM, Soares SLM, Mello FCQ, Reingold AL, et al. Yield of sputum induction in the diagnosis of pleural tuberculosis. Am J Respir Crit Care Med. 2003;167:723\u20135.","journal-title":"Am J Respir Crit Care Med"},{"key":"5676_CR2","doi-asserted-by":"publisher","first-page":"ii4","DOI":"10.1136\/thx.2010.136978","volume":"65","author":"C Hooper","year":"2010","unstructured":"Hooper C, Lee YCG, Maskell N. Investigation of a unilateral pleural effusion in adults: British Thoracic Society pleural disease guideline 2010. Thorax. 2010;65:ii4\u2013ii17.","journal-title":"Thorax."},{"key":"5676_CR3","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1183\/09031936.03.00051603","volume":"21","author":"D Jim\u00e9nez Castro","year":"2003","unstructured":"Jim\u00e9nez Castro D, D\u00edaz Nuevo G, P\u00e9rez-Rodr\u00edguez E, Light RW. Diagnostic value of adenosine deaminase in nontuberculous lymphocytic pleural effusions. Eur Respir J. 2003;21:220\u20134.","journal-title":"Eur Respir J"},{"key":"5676_CR4","doi-asserted-by":"publisher","first-page":"e0213728","DOI":"10.1371\/journal.pone.0213728","volume":"14","author":"AN Aggarwal","year":"2019","unstructured":"Aggarwal AN, Agarwal R, Sehgal IS, Dhooria S. Adenosine deaminase for diagnosis of tuberculous pleural effusion: a systematic review and meta-analysis. Eapen GA, editor. PLoS One. 2019;14:e0213728. https:\/\/doi.org\/10.1371\/journal.pone.0213728.","journal-title":"PLoS One"},{"key":"5676_CR5","doi-asserted-by":"publisher","first-page":"880","DOI":"10.1378\/chest.06-2063","volume":"131","author":"A Gopi","year":"2007","unstructured":"Gopi A, Madhavan SM, Sharma SK, Sahn SA. Diagnosis and treatment of tuberculous pleural effusion in 2006. Chest. The American College of Chest Physicians. 2007;131:880\u20139. https:\/\/doi.org\/10.1378\/chest.06-2063.","journal-title":"Chest"},{"key":"5676_CR6","doi-asserted-by":"publisher","first-page":"1924","DOI":"10.1080\/21691401.2019.1613417","volume":"47","author":"X Yang","year":"2019","unstructured":"Yang X, Feng M, Shen Y, Deng B, He Y, Cao G. Clinical characteristics and potential indicators for definite diagnosis of tuberculous pleural effusion. Artif Cells Nanomed Biotechnol. 2019;47:1924\u201331.","journal-title":"Artif Cells Nanomed Biotechnol"},{"key":"5676_CR7","doi-asserted-by":"publisher","first-page":"697","DOI":"10.5588\/ijtld.16.0803","volume":"21","author":"P Sivakumar","year":"2017","unstructured":"Sivakumar P, Marples L, Breen R, Ahmed L. The diagnostic utility of pleural fluid adenosine deaminase for tuberculosis in a low prevalence area. Int J Tuberc Lung Dis. 2017;21:697\u2013701.","journal-title":"Int J Tuberc Lung Dis"},{"key":"5676_CR8","unstructured":"WHO World Health Organization. Strategic and technical advisory group for tuberculosis (STAG-TB). Report of the 10th meeting 27\u201329 Sept. 2010. Rep Tenth Meet 2010; (September)."},{"key":"5676_CR9","doi-asserted-by":"publisher","unstructured":"ECDC. Use of interferon-gamma release assays in support of TB diagnosis. Eur Cent Dis Prev Control. 2011.\u00a0https:\/\/doi.org\/10.2900\/38588.","DOI":"10.2900\/38588"},{"key":"5676_CR10","first-page":"1","volume":"2015","author":"CS Pang","year":"2015","unstructured":"Pang CS, Shen YC, Tian PW, Zhu J, Feng M, Wan C, et al. Accuracy of the interferon-gamma release assay for the diagnosis of tuberculous pleurisy: an updated meta-analysis. PeerJ. 2015;2015:1\u201317.","journal-title":"PeerJ."},{"key":"5676_CR11","first-page":"259","volume":"9","author":"RL Soiza","year":"2018","unstructured":"Soiza RL, Donaldson AIC, Myint PK. Vaccine against arteriosclerosis: an update. Ther Adv Vaccines. 2018;9:259\u201361.","journal-title":"Ther Adv Vaccines"},{"key":"5676_CR12","volume-title":"Technicalguide: sputum examination for tuberculosis by direct microscopy in low income countries","author":"International Union against Tuberculosis and Lung Disease","year":"2000","unstructured":"International Union against Tuberculosis and Lung Disease. Technicalguide: sputum examination for tuberculosis by direct microscopy in low income countries. 5th ed. Paris: International Union against Tuberculosis and Lung Disease; 2000.","edition":"5"},{"key":"5676_CR13","doi-asserted-by":"publisher","first-page":"1118","DOI":"10.1183\/09031936.00005309","volume":"34","author":"K Dheda","year":"2009","unstructured":"Dheda K, Van Zyl-Smit RN, Sechi LA, Badri M, Meldau R, Meldau S, et al. Utility of quantitative T-cell responses versus unstimulated interferon-\u03b3 for the diagnosis of pleural tuberculosis. Eur Respir J. 2009;34:1118\u201326.","journal-title":"Eur Respir J"},{"key":"5676_CR14","doi-asserted-by":"publisher","first-page":"1446","DOI":"10.1373\/clinchem.2015.246280","volume":"61","author":"PM Bossuyt","year":"2015","unstructured":"Bossuyt PM, Reitsma JB, Bruns DE, Gatsonis CA, Glasziou PP, Irwig L, et al. STARD 2015: an updated list of essential items for reporting diagnostic accuracy studies. Clin Chem. 2015;61:1446\u201352.","journal-title":"Clin Chem"},{"key":"5676_CR15","doi-asserted-by":"publisher","first-page":"457","DOI":"10.3201\/eid2503.180572","volume":"25","author":"Y Pang","year":"2019","unstructured":"Pang Y, An J, Shu W, Huo F, Chu N, Gao M, et al. Epidemiology of extrapulmonary tuberculosis among inpatients, China, 2008-2017. Emerg Infect Dis. 2019;25:457\u201364.","journal-title":"Emerg Infect Dis"},{"key":"5676_CR16","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1136\/emj.20.1.6","volume":"20","author":"S Cooper","year":"2003","unstructured":"Cooper S, Evans C. Resuscitation predictor scoring scale for inhospital cardiac arrests. Emerg Med J. 2003;20:6\u20139.","journal-title":"Emerg Med J"},{"key":"5676_CR17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12879-018-3567-x","volume":"19","author":"Y Tang","year":"2019","unstructured":"Tang Y, Zhang J, Huang H, He X, Zhang J, Ou M, et al. Pleural IFN-\u03b3 release assay combined with biomarkers distinguished effectively tuberculosis from malignant pleural effusion. BMC Infect Dis. 2019;19:1\u20138.","journal-title":"BMC Infect Dis"},{"key":"5676_CR18","doi-asserted-by":"publisher","first-page":"1173","DOI":"10.1183\/09031936.00067307","volume":"30","author":"M Losi","year":"2007","unstructured":"Losi M, Bossink A, Codecasa L, Jafari C, Ernst M, Thijsen S, et al. Use of a T-cell interferon-\u03b3 release assay for the diagnosis of tuberculous pleurisy. Eur Respir J. 2007;30:1173\u20139.","journal-title":"Eur Respir J"},{"key":"5676_CR19","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1086\/426139","volume":"40","author":"KA Wilkinson","year":"2005","unstructured":"Wilkinson KA, Wilkinson RJ, Pathan A, Ewer K, Prakash M, Klenerman P, et al. Ex vivo characterization of early secretory antigenic target 6-specific T cells at sites of active disease in pleural tuberculosis. Clin Infect Dis. 2005;40:184\u20137.","journal-title":"Clin Infect Dis"},{"key":"5676_CR20","doi-asserted-by":"publisher","first-page":"143","DOI":"10.4046\/trd.2012.73.3.143","volume":"73","author":"JY Kang","year":"2012","unstructured":"Kang JY, Rhee CK, Kang NH, Kim JS, Yoon HK, Song JS. Clinical utility of two interferon-gamma release assays on pleural fluid for the diagnosis of tuberculous pleurisy. Tuberc Respir Dis (Seoul). 2012;73:143\u201350.","journal-title":"Tuberc Respir Dis (Seoul)"},{"key":"5676_CR21","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1128\/JCM.00258-18","volume":"56","author":"M Blakiston","year":"2018","unstructured":"Blakiston M, Chiu W, Wong C, Morpeth S, Taylor S. Diagnostic performance of pleural fluid adenosine deaminase for tuberculous pleural effusion in a low-incidence setting. J Clin Microbiol. 2018;56:1\u20138.","journal-title":"J Clin Microbiol"},{"key":"5676_CR22","doi-asserted-by":"publisher","first-page":"e0202481","DOI":"10.1371\/journal.pone.0202481","volume":"13","author":"AP Santos","year":"2018","unstructured":"Santos AP, Correa RDS, Ribeiro-Alves M, Soares da Silva ACO, Mafort TT, Leung J, et al. Application of Venn\u2019s diagram in the diagnosis of pleural tuberculosis using IFN-gamma, IP-10 and adenosine deaminase. PLoS One. 2018;13:e0202481.","journal-title":"PLoS One"},{"key":"5676_CR23","doi-asserted-by":"publisher","first-page":"134","DOI":"10.4103\/atm.ATM_359_18","volume":"14","author":"TT Zhao","year":"2019","unstructured":"Zhao TT, Xu YR, Song Q, Wang XJ, Jin MH, Lin DJ. Medical thoracoscopy for tuberculous pleurisy: a retrospective analysis of 575 cases. Ann Thorac Med. 2019;14:134\u201340.","journal-title":"Ann Thorac Med"},{"key":"5676_CR24","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1016\/j.jinf.2013.05.009","volume":"67","author":"LT Keng","year":"2013","unstructured":"Keng LT, Shu CC, Chen JYP, Liang SK, Lin CK, Chang LY, et al. Evaluating pleural ADA, ADA2, IFN-\u03b3 and IGRA for diagnosing tuberculous pleurisy. J Infect. Elsevier Ltd. 2013;67:294\u2013302. https:\/\/doi.org\/10.1016\/j.jinf.2013.05.009.","journal-title":"J Infect"},{"key":"5676_CR25","doi-asserted-by":"publisher","first-page":"3272","DOI":"10.1080\/21691401.2019.1647221","volume":"47","author":"M Feng","year":"2019","unstructured":"Feng M, Sun F, Wang F, Cao G. The diagnostic effect of sequential detection of ADA screening and T-SPOT assay in pleural effusion patients. Artif Cells Nanomed Biotechnol. Taylor & Francis. 2019;47:3272\u20137. https:\/\/doi.org\/10.1080\/21691401.2019.1647221.","journal-title":"Artif Cells Nanomed Biotechnol"}],"container-title":["BMC Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12879-020-05676-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12879-020-05676-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12879-020-05676-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,1,4]],"date-time":"2021-01-04T10:04:32Z","timestamp":1609754672000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcinfectdis.biomedcentral.com\/articles\/10.1186\/s12879-020-05676-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,4]]},"references-count":25,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["5676"],"URL":"https:\/\/doi.org\/10.1186\/s12879-020-05676-2","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.2.22951\/v3","asserted-by":"object"},{"id-type":"doi","id":"10.21203\/rs.2.22951\/v2","asserted-by":"object"},{"id-type":"doi","id":"10.21203\/rs.2.22951\/v5","asserted-by":"object"},{"id-type":"doi","id":"10.21203\/rs.2.22951\/v4","asserted-by":"object"},{"id-type":"doi","id":"10.21203\/rs.2.22951\/v1","asserted-by":"object"}]},"ISSN":["1471-2334"],"issn-type":[{"value":"1471-2334","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,4]]},"assertion":[{"value":"3 February 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 November 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 January 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"We complied with the World Medical Association Declaration of Helsinki regarding ethical guidelines involving human subjects. The study protocol was approved by the Ethics Committee of the Beijing chest Hospital affiliated with Capital Medical University, China. We obtained written informed consent from all participants, and the consent of the participants below age 18\u2009years were obtained from their guardian.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"JZ is an Associate Editor at BMC Infectious Diseases. All other authors have no any possible competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"4"}}