{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T15:52:19Z","timestamp":1790610739497,"version":"4.1.0"},"reference-count":38,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2022,7,8]],"date-time":"2022-07-08T00:00:00Z","timestamp":1657238400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100015690","name":"Universitas Padjadjaran","doi-asserted-by":"publisher","award":["1959\/UN6.3.1\/PT.00\/2021"],"award-info":[{"award-number":["1959\/UN6.3.1\/PT.00\/2021"]}],"id":[{"id":"10.13039\/501100015690","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Interferon gamma release assays (IGRAs) are widely used to determine latent tuberculosis infection status. However, its pregnancy-affected performance and cost-expensive nature warrants for different alternatives for pregnant women. This study aims to evaluate the diagnostic performance of several alternative cytokines, including interleukin 2 (IL-2), interleukin 10 (IL-10), and interferon gamma-induced protein 10 (IP-10) to identify latent tuberculosis status in pregnant women.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Materials and methods<\/jats:title>\n<jats:p>123 pregnant womens were recruited for this study. The IGRA status was determined by using QuantiFERON Gold In-Tube. Meanwhile, we measured the level IL-2, IL-10, and IP-10 by using sandwich-microELISA method. We performed normality and comparison test by SPSS. In addition, receiver-operator characteristic (ROC) analyses and the optimal cutoff scores were identified using the EasyROC webtool.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>We showed that IL-2, IL-10, and IP-10 were able to discriminate between IGRA-negative and IGRA-positive pregnant women. Moreover, IP-10 showed the highest discriminatory and diagnostic performance when compared to IL-2 and IL-10 with area under the curve (AUC) of 0.96 and cutoff point of 649.65 pg\/mL.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Our study showed that IP-10 can be considered as a promising alternative biomarker for IGRAs to diagnose LTBI in pregnant women.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0270552","type":"journal-article","created":{"date-parts":[[2022,7,8]],"date-time":"2022-07-08T18:05:48Z","timestamp":1657303548000},"page":"e0270552","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":14,"title":["Exploring alternative cytokines as potential biomarkers for latent tuberculosis infection in pregnant women"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3923-9767","authenticated-orcid":true,"given":"Agnes Rengga","family":"Indrati","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5196-4510","authenticated-orcid":true,"given":"Anton","family":"Sumarpo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0636-6057","authenticated-orcid":true,"given":"Petty","family":"Atmadja","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rositha Ratna","family":"Wisesa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9392-8374","authenticated-orcid":true,"given":"Mohammad","family":"Ghozali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raden Tina Dewi","family":"Judistiani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4842-2451","authenticated-orcid":true,"given":"Budi","family":"Setiabudiawan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,7,8]]},"reference":[{"key":"pone.0270552.ref001","article-title":"Global Tuberculosis Report 2020 \u2013Reflections on the Global TB burden, treatment and prevention efforts","author":"J Chakaya","year":"2021","journal-title":"International Journal of Infectious Diseases"},{"key":"pone.0270552.ref002","doi-asserted-by":"crossref","DOI":"10.1016\/S2214-109X(14)70330-4","article-title":"Tuberculosis in pregnancy: An estimate of the global burden of disease","volume":"2","author":"J Sugarman","year":"2014","journal-title":"The Lancet Global Health"},{"key":"pone.0270552.ref003","unstructured":"World Health Organization. Global tuberculosis report 2018. World Health Organization. World Health Organization. 2018."},{"key":"pone.0270552.ref004","doi-asserted-by":"crossref","DOI":"10.1186\/s12889-020-8419-0","article-title":"Global trends and gaps in research related to latent tuberculosis infection","volume":"20","author":"L Chaw","year":"2020","journal-title":"BMC Public Health"},{"key":"pone.0270552.ref005","article-title":"Latent tuberculosis in pregnancy: A systematic review","author":"I Malham\u00e9","year":"2016","journal-title":"PLoS ONE"},{"key":"pone.0270552.ref006","article-title":"Diagnosis and treatment of latent tuberculosis infection","author":"SH Lee","year":"2015","journal-title":"Tuberculosis and Respiratory Diseases"},{"key":"pone.0270552.ref007","article-title":"Tuberculosis and latent tuberculosis infection in close contacts of people with pulmonary tuberculosis in low-income and middle-income countries: a systematic review and meta-analysis","author":"J Morrison","year":"2008","journal-title":"The Lancet Infectious Diseases"},{"key":"pone.0270552.ref008","doi-asserted-by":"crossref","DOI":"10.1186\/s12879-017-2301-4","article-title":"Comparing interferon-gamma release assays with tuberculin skin test for identifying latent tuberculosis infection that progresses to active tuberculosis: Systematic review and meta-analysis","volume":"17","author":"P Auguste","year":"2017","journal-title":"BMC Infectious Diseases"},{"key":"pone.0270552.ref009","article-title":"Diagnosis for Latent Tuberculosis Infection: New Alternatives","author":"C Carranza","year":"2020","journal-title":"Frontiers in Immunology"},{"key":"pone.0270552.ref010","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0169539","article-title":"Comparison of TST and IGRA in diagnosis of latent tuberculosis infection in a high TB-burden setting","volume":"12","author":"SK Sharma","year":"2017","journal-title":"PLoS ONE"},{"key":"pone.0270552.ref011","unstructured":"WHO. Use of tuberculosis release assays (IGRAs) in low and middle-income countries. World Health Organization Policy Statement. 2011."},{"key":"pone.0270552.ref012","doi-asserted-by":"crossref","DOI":"10.1164\/rccm.201508-1595OC","article-title":"Quantitative IFN-\u03b3 and IL-2 response associated with latent tuberculosis test discordance in HIV-infected pregnant women","volume":"193","author":"JS Mathad","year":"2016","journal-title":"American Journal of Respiratory and Critical Care Medicine"},{"key":"pone.0270552.ref013","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0092308","article-title":"Pregnancy differentially impacts performance of latent tuberculosis diagnostics in a high-burden setting","volume":"9","author":"JS Mathad","year":"2014","journal-title":"PLoS ONE"},{"key":"pone.0270552.ref014","doi-asserted-by":"crossref","DOI":"10.1097\/QAI.0000000000001298","article-title":"Effect of pregnancy on interferongammarelease assay and tuberculin skin test detection of latent tb infection among HIV-infected women in a high burden setting","volume":"75","author":"SM LaCourse","year":"2017","journal-title":"Journal of Acquired Immune Deficiency Syndromes"},{"key":"pone.0270552.ref015","doi-asserted-by":"crossref","DOI":"10.1016\/j.tube.2020.101984","article-title":"Alternative biomarkers for classification of latent tuberculosis infection status in pregnant women with borderline Quantiferon plus results","volume":"124","author":"F Tesfaye","year":"2020","journal-title":"Tuberculosis"},{"key":"pone.0270552.ref016","doi-asserted-by":"crossref","DOI":"10.3109\/00365548.2011.632644","article-title":"Interferon-gamma inducible protein 10 as a biomarker for active tuberculosis and latent tuberculosis infection in children: A case-control study","volume":"44","author":"N Alsleben","year":"2012","journal-title":"Scandinavian Journal of Infectious Diseases"},{"key":"pone.0270552.ref017","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0146098","article-title":"The use of interferon gamma inducible protein 10 as a potential biomarker in the diagnosis of latent tuberculosis infection in Uganda","volume":"11","author":"IA Biraro","year":"2016","journal-title":"PLoS ONE"},{"key":"pone.0270552.ref018","doi-asserted-by":"crossref","DOI":"10.1016\/j.tube.2018.06.005","article-title":"Evaluation of IP-10 in Quantiferon-Plus as biomarker for the diagnosis of latent tuberculosis infection","volume":"111","author":"L Petrone","year":"2018","journal-title":"Tuberculosis"},{"key":"pone.0270552.ref019","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0003901","article-title":"Is IP-10 a better biomarker for active and latent tuberculosis in children than IFN\u03b3?","volume":"3","author":"E Whittaker","year":"2008","journal-title":"PLoS ONE"},{"key":"pone.0270552.ref020","article-title":"IP-10 release assays in the diagnosis of tuberculosis infection: Current status and future directions","author":"M Ruhwald","year":"2012","journal-title":"Expert Review of Molecular Diagnostics"},{"key":"pone.0270552.ref021","article-title":"IL-2 production in developing Th1 cells is regulated by heterodimerization of RelA and T-bet and requires T-bet serine residue 508","volume":"202","author":"SH Eun","year":"2005","journal-title":"Journal of Experimental Medicine"},{"key":"pone.0270552.ref022","article-title":"Potential role for Mycobacterium tuberculosis specific IL-2 and IFN-\u03b3 responses in discriminating between latent infection and active disease after long-term stimulation","volume":"11","author":"Q Sun","year":"2016","journal-title":"PLoS ONE"},{"key":"pone.0270552.ref023","article-title":"Combined IFN-\u03b3 and IL-2 release assay for detect active pulmonary tuberculosis: a prospective multicentre diagnostic study in China","volume":"19","author":"Y Tan","year":"2021","journal-title":"Journal of Translational Medicine"},{"key":"pone.0270552.ref024","doi-asserted-by":"crossref","DOI":"10.1111\/j.1469-0691.2009.03104.x","article-title":"Detection of interleukin-2 in addition to interferon-\u03b3 discriminates active tuberculosis patients, latently infected individuals, and controls","volume":"16","author":"R Biselli","year":"2010","journal-title":"Clinical Microbiology and Infection"},{"key":"pone.0270552.ref025","doi-asserted-by":"crossref","DOI":"10.4049\/jimmunol.169.11.6343","article-title":"In Vivo IL-10 Production Reactivates Chronic Pulmonary Tuberculosis in C57BL\/6 Mice","volume":"169","author":"J Turner","year":"2002","journal-title":"The Journal of Immunology"},{"key":"pone.0270552.ref026","article-title":"Evaluation of the Diagnostic Potential of IP-10 and IL-2 as Biomarkers for the Diagnosis of Active and Latent Tuberculosis in a BCG-Vaccinated Population","volume":"7","author":"S Wang","year":"2012","journal-title":"PLoS ONE"},{"key":"pone.0270552.ref027","unstructured":"Qiagen. QuantiFERON-TB Gold Plus ELISA Package Insert. 2019 [cited 14 Feb 2022]. http:\/\/www.quantiferon.com\/wp-content\/uploads\/2017\/04\/English_QFTPlus_ELISA_R04_022016.pdf"},{"key":"pone.0270552.ref028","unstructured":"Elabscience. Human IL-10 (Interleukin 10) ELISA Kit. 2021 [cited 16 Feb 2022]. https:\/\/file.elabscience.com\/Manual\/elisa_kits\/E-EL-H6154.pdf"},{"key":"pone.0270552.ref029","unstructured":"Elabscience. Human IL-2 (Interleukin 2) ELISA Kit. 2021 [cited 16 Feb 2022]. https:\/\/u2.elabscience.com\/PDF\/Cate61\/E-EL-H0099-Elabscience.pdf"},{"key":"pone.0270552.ref030","unstructured":"Elabscience. Human IP-10\/CXCL10 (Interferon Gamma Induced Protein 10kDa) ELISA Kit. 2021 [cited 16 Feb 2022]. https:\/\/u2.elabscience.com\/PDF\/Cate61\/E-EL-H0050-Elabscience.pdf"},{"key":"pone.0270552.ref031","doi-asserted-by":"crossref","DOI":"10.32614\/RJ-2016-042","article-title":"EasyROC: An interactive web-tool for roc curve analysis using r language environment","volume":"8","author":"D Goksuluk","year":"2016","journal-title":"R Journal"},{"key":"pone.0270552.ref032","doi-asserted-by":"crossref","DOI":"10.1007\/s12026-012-8303-9","article-title":"The influence of pregnancy on systemic immunity","volume":"54","author":"M Pazos","year":"2012","journal-title":"Immunologic Research"},{"key":"pone.0270552.ref033","article-title":"Interferons and Proinflammatory Cytokines in Pregnancy and Fetal Development","author":"LJ Yockey","year":"2018","journal-title":"Immunity"},{"key":"pone.0270552.ref034","article-title":"Maternal Immunological Adaptation During Normal Pregnancy","author":"B Abu-Raya","year":"2020","journal-title":"Frontiers in Immunology"},{"key":"pone.0270552.ref035","doi-asserted-by":"crossref","DOI":"10.1159\/000010165","article-title":"Interferon gamma expression during human pregnancy and in association with labour","volume":"48","author":"GL Veith","year":"1999","journal-title":"Gynecologic and Obstetric Investigation"},{"key":"pone.0270552.ref036","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0152483","article-title":"Combined analysis of IFN-\u03b3, IL-2, IL-5, IL-10, IL-1RA and MCP-1 in QFT supernatant is useful for distinguishing active tuberculosis from latent infection","volume":"11","author":"M Suzukawa","year":"2016","journal-title":"PLoS ONE"},{"key":"pone.0270552.ref037","doi-asserted-by":"crossref","DOI":"10.1016\/j.jinf.2014.12.019","article-title":"IP-10 differentiates between active and latent tuberculosis irrespective of HIV status and declines during therapy","volume":"70","author":"I Wergeland","year":"2015","journal-title":"Journal of Infection"},{"key":"pone.0270552.ref038","article-title":"Accuracy of interferon-\u03b3-induced protein 10 for diagnosing latent tuberculosis infection: a systematic review and meta-analysis","author":"X Qiu","year":"2019","journal-title":"Clinical Microbiology and Infection"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0270552","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,8]],"date-time":"2022-07-08T18:06:51Z","timestamp":1657303611000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0270552"}},"subtitle":[],"editor":[{"given":"Wenping","family":"Gong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,7,8]]},"references-count":38,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2022,7,8]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0270552","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,8]]}}}