{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T03:05:17Z","timestamp":1783998317905,"version":"3.55.0"},"reference-count":21,"publisher":"International Union Against Tuberculosis and Lung Disease","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJTLD Open"],"accepted":{"date-parts":[[2026,3,3]]},"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>SUMMARY<\/jats:title>\n                  <jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>\n                      Distinguishing TB infection (TBI) from TB disease remains difficult because routine tests, including tuberculin skin test and interferon-gamma release assay (IGRA), cannot separate these states. We assessed a flow cytometry\u2013based assay that measures T-cell cytokine responses after stimulation with\n                      <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      We enrolled 118 IGRA-positive participants, including individuals with TB\/TBI. Individuals were grouped by age and disease category into paediatric\/adult TB, TBI, and immunocompromised TBI. Peripheral blood lymphocytes were stimulated with ESAT-6\/CFP-10 antigens under CD4\n                      <jats:sup>+<\/jats:sup>\n                      -focused (TB1) or combined CD4\n                      <jats:sup>+<\/jats:sup>\n                      \/CD8\n                      <jats:sup>+<\/jats:sup>\n                      (TB2) conditions. Intracellular IL-10, IL-2, and tumour necrosis factor-\u03b1 (TNF-\u03b1) were quantified by flow cytometry. Cytokine levels were compared using Mann\u2013Whitney\n                      <jats:italic>U<\/jats:italic>\n                      tests.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Among children, most cytokine responses overlapped between TBI and TB, except TNF-\u03b1 in CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells after TB2 stimulation, which was higher in TB. In adults, IL-10 in CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells was elevated in TBI after TB1 and TB2 stimulation, whereas IL-2 in CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells was higher in TB after TB2 stimulation. TNF-\u03b1 did not differentiate groups in adults.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>\n                      Flow-cytometric cytokine profiling may help distinguish TBI from TB, with age-specific markers. TNF-\u03b1 in CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells appears informative in children, while IL-10 and IL-2 in CD4\n                      <jats:sup>+<\/jats:sup>\n                      T cells show promise in adults. Further validation is needed.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.5588\/ijtldopen.25.0781","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T02:33:43Z","timestamp":1783996423000},"page":"421-427","source":"Crossref","is-referenced-by-count":0,"title":["Refining cytokine signatures: flow cytometry\u2013based differentiation between TB infection and disease"],"prefix":"10.5588","volume":"3","author":[{"given":"K.","family":"Dole\u017ealov\u00e1","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Goli\u00e1\u0161","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Ibrahimov\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Ba\u010da","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Kopeck\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.","family":"Hricikov\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Rajnochov\u00e1-Bloud\u00ed\u010dkov\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Philipp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Koziar Va\u0161\u00e1kov\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"3554","published-online":{"date-parts":[[2026,7,1]]},"reference":[{"key":"2026071319333507000_3.7.421.1","unstructured":"World Health Organization . Global Tuberculosis Report 2025. Geneva: WHO, 2025."},{"key":"2026071319333507000_3.7.421.2","first-page":"230","article-title":"TB in the immunocompromised host","volume":"58","author":"Sester","year":"2025","journal-title":"Eur Respir Monogr"},{"key":"2026071319333507000_3.7.421.3","doi-asserted-by":"crossref","first-page":"100763","DOI":"10.1016\/j.ijregi.2025.100763","article-title":"Differences found in patient profiles and incidence trends between migrants and native-born tuberculosis patients in Ireland: a cross-sectional analysis of national surveillance data, 2011-2021","volume":"17","author":"Jackson","year":"2025","journal-title":"IJID Reg"},{"issue":"2","key":"2026071319333507000_3.7.421.4","doi-asserted-by":"crossref","first-page":"106","DOI":"10.5588\/ijtld.23.0292","article-title":"Increasing incidence of TB in a low burden TB country due to migration from Ukraine","volume":"28","author":"Dole\u017ealov\u00e1","year":"2024","journal-title":"Int J Tuberc Lung Dis"},{"issue":"5","key":"2026071319333507000_3.7.421.5","doi-asserted-by":"crossref","first-page":"E684","DOI":"10.1016\/S2214-109X(23)00082-7","article-title":"The natural history of TB disease-a synthesis of data to quantify progression and regression across the spectrum","volume":"11","author":"Richards","year":"2023","journal-title":"Lancet Glob Health"},{"key":"2026071319333507000_3.7.421.6","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00028510"},{"issue":"3","key":"2026071319333507000_3.7.421.7","first-page":"235","article-title":"Tuberculosis infection under anti-TNF alpha treatment","volume":"17","author":"Athimni","year":"2021","journal-title":"Curr Drug Saf"},{"key":"2026071319333507000_3.7.421.8","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00076714"},{"key":"2026071319333507000_3.7.421.9","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12066"},{"key":"2026071319333507000_3.7.421.10","doi-asserted-by":"crossref","first-page":"102518","DOI":"10.1016\/j.tube.2024.102518","article-title":"Flow cytometry-based method using diversity of cytokine production differentiates between Mycobacterium tuberculosis infection and disease","volume":"147","author":"Dolezalova","year":"2024","journal-title":"Tuberculosis"},{"key":"2026071319333507000_3.7.421.11","unstructured":"Institute of Health Information and Statistics of the Czech Republic . Basic Overview of Tuberculosis Epidemiology in the Czech Republic in 2024. Prague, Czech Republic: Institute of Health Information and Statistics of the Czech Republic, 2025. https:\/\/www.uzis.cz\/res\/f\/008462\/tbc2024-en.pdf (Accessed 2 June 2026)."},{"key":"2026071319333507000_3.7.421.12","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0138952"},{"issue":"3","key":"2026071319333507000_3.7.421.13","doi-asserted-by":"crossref","first-page":"e0097221","DOI":"10.1128\/Spectrum.00972-21","article-title":"Identification of recent tuberculosis exposure using QuantiFERON-TB Gold Plus, a multicenter study","volume":"9","author":"P\u00e9rez-Recio","year":"2021","journal-title":"Microbiol Spectr"},{"key":"2026071319333507000_3.7.421.14","doi-asserted-by":"publisher","DOI":"10.1016\/S0163-4453(17)30195-0"},{"key":"2026071319333507000_3.7.421.15","unstructured":"World Health Organization . WHO consolidated guidelines on tuberculosis. Module 4: treatment - drug-resistant tuberculosis treatment, 2022 update. Geneva: WHO, 2022."},{"issue":"11","key":"2026071319333507000_3.7.421.16","doi-asserted-by":"crossref","first-page":"E307","DOI":"10.1097\/INF.0000000000002416","article-title":"Borderline-positive quantiferon in children","volume":"38","author":"Nygaard","year":"2019","journal-title":"Pediatr Infect Dis J"},{"issue":"7","key":"2026071319333507000_3.7.421.17","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1097\/INF.0000000000002606","article-title":"False-positive results of Quantiferon-Tb-Gold assay in children","volume":"39","author":"Quintana-Ortega","year":"2020","journal-title":"Pediatr Infect Dis J"},{"key":"2026071319333507000_3.7.421.18","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.jim.2014.07.013","article-title":"Long-term IFN-\u03b3 and IL-2 response for detection of latent tuberculosis infection in healthcare workers with discordant immunologic results","volume":"414","author":"Sauzullo","year":"2014","journal-title":"J Immunol Methods"},{"key":"2026071319333507000_3.7.421.19","doi-asserted-by":"crossref","first-page":"215084","DOI":"10.3389\/fimmu.2016.00421","article-title":"Increased TNF-\u03b1\/IFN-\u03b3\/IL-2 and decreased TNF-\u03b1\/IFN-\u03b3 production by central memory T cells are associated with protective responses against bovine tuberculosis following BCG vaccination","volume":"7","author":"Maggioli","year":"2016","journal-title":"Front Immunol"},{"key":"2026071319333507000_3.7.421.20","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201501-0059OC"},{"key":"2026071319333507000_3.7.421.21","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2013.02.004"}],"container-title":["IJTLD Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.5588\/ijtldopen.25.0781","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T02:33:46Z","timestamp":1783996426000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.theunion.org\/lookup\/doi\/10.5588\/ijtldopen.25.0781"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7]]},"references-count":21,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7,1]]},"published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.5588\/ijtldopen.25.0781"],"URL":"https:\/\/doi.org\/10.5588\/ijtldopen.25.0781","relation":{},"ISSN":["3005-7590"],"issn-type":[{"value":"3005-7590","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7]]}}}