{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T19:16:37Z","timestamp":1786648597034,"version":"build-2736575974"},"reference-count":38,"publisher":"European Respiratory Society (ERS)","issue":"2","license":[{"start":{"date-parts":[[2022,1,20]],"date-time":"2022-01-20T00:00:00Z","timestamp":1642636800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010661","name":"Horizon 2020 Framework Programme","doi-asserted-by":"publisher","award":["TBVAC2020 consortium (no. 643381)"],"award-info":[{"award-number":["TBVAC2020 consortium (no. 643381)"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["publications.ersnet.org"],"crossmark-restriction":true},"short-container-title":["Eur Respir J"],"accepted":{"date-parts":[[2021,12,18]]},"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Screening for tuberculosis (TB) infection often includes QuantiFERON-TB Gold Plus (QFT) testing. Previous studies showed that two-thirds of patients with negative QFT results just below the cut-off, so-called borderline test results, nevertheless had other evidence of TB infection. This study aimed to identify a biomarker profile by which borderline QFT results due to TB infection can be distinguished from random test variation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>QFT supernatants of patients with a borderline (\u22650.15 and &lt;0.35\u2005IU\u00b7mL<jats:sup>\u22121<\/jats:sup>), low-negative (&lt;0.15\u2005IU\u00b7mL<jats:sup>\u22121<\/jats:sup>) or positive (\u22650.35\u2005IU\u00b7mL<jats:sup>\u22121<\/jats:sup>) QFT result were collected in three hospitals. Bead-based multiplex assays were used to analyse 48 different cytokines, chemokines and growth factors. A prediction model was derived using LASSO regression and applied further to discriminate QFT-positive<jats:italic>Mycobacterium tuberculosis<\/jats:italic>-infected patients from borderline QFT patients and QFT-negative patients<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>QFT samples of 195 patients were collected and analysed. Global testing revealed that the levels of 10\u2005kDa interferon (IFN)-\u03b3-induced protein (IP-10\/CXCL10), monokine induced by IFN-\u03b3 (MIG\/CXCL9) and interleukin-1 receptor antagonist in the antigen-stimulated tubes were each significantly higher in patients with a positive QFT result compared with low-negative QFT individuals (p&lt;0.001). A prediction model based on IP-10 and MIG proved highly accurate in discriminating patients with a positive QFT (TB infection) from uninfected individuals with a low-negative QFT (sensitivity 1.00 (95% CI 0.79\u20131.00) and specificity 0.95 (95% CI 0.74\u20131.00)). This same model predicted TB infection in 68% of 87 patients with a borderline QFT result.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study was able to classify borderline QFT results as likely infection-related or random. These findings support additional laboratory testing for either IP-10 or MIG following a borderline QFT result for individuals at increased risk of reactivation TB.<\/jats:p><\/jats:sec>","DOI":"10.1183\/13993003.02665-2021","type":"journal-article","created":{"date-parts":[[2022,1,20]],"date-time":"2022-01-20T17:06:02Z","timestamp":1642698362000},"page":"2102665","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":22,"title":["Biomarkers to identify<i>Mycobacterium tuberculosis<\/i>infection among borderline QuantiFERON results"],"prefix":"10.1183","volume":"60","author":[{"given":"Jonathan W.","family":"Uzorka","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2918-7361","authenticated-orcid":false,"given":"Jaap A.","family":"Bakker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krista 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