{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T18:33:06Z","timestamp":1763058786950,"version":"3.40.5"},"reference-count":39,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,9,26]],"date-time":"2022-09-26T00:00:00Z","timestamp":1664150400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cytometry Part B Clinical"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The interferon\u2010<jats:italic>\u03b3<\/jats:italic>(IFN\u2010<jats:italic>\u03b3<\/jats:italic>) release assay (IGRA) is widely used to diagnose tuberculosis (TB) caused by<jats:italic>Mycobacterium tuberculosis<\/jats:italic>(Mtb). However, indeterminate IGRA results due to \u201chigh Nil\u201d or \u201clow PHA\u201d responses limit its clinical utility. We developed a novel assay using CD69 flow cytometry (FC) to complement IGRA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>CD69 FC measures the surface CD69 expression on T cells prior to centrifugation to harvest the plasma for IGRA. T cell responses against Mtb antigen 1 (Ag1) or Ag2 were measured using three\u2010color FC (CD3, CD4, and CD69) in TB (n\u00a0=\u00a0140) and non\u2010TB groups (n\u00a0=\u00a0117). The cutoff values of \u0394%CD69<jats:sup>bright<\/jats:sup>cells (stimulated minus unstimulated) for CD4<jats:sup>+<\/jats:sup>and CD4<jats:sup>\u2212<\/jats:sup>T cells were established based on healthy individuals (n\u00a0=\u00a063). The assay performances of CD69 FC and IGRA were compared.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In subjects with determinate IGRA results (\u201cpositive\u201d or \u201cnegative\u201d; n\u00a0=\u00a0216), the diagnostic accuracies of CD69 FC (90.3%) and IGRA (87.0%) were not significantly different (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.31). For indeterminate IGRA results (n\u00a0=\u00a040), CD69 FC attained a diagnostic accuracy of 92.5%. The CD4<jats:sup>+<\/jats:sup>\/CD4<jats:sup>\u2212<\/jats:sup>ratio within CD69<jats:sup>bright<\/jats:sup>T cells measured by CD69 FC was significantly higher (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) in the active TB group (6.39\u2009\u00b1\u2009132.05; n\u00a0=\u00a072) than in other CD69 FC\u2010positive subjects (2.84\u2009\u00b1\u200915.36; n\u00a0=\u00a063) (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05), whereas CD8 responses expected by IGRA (difference of IFN\u2010<jats:italic>\u03b3<\/jats:italic>levels between Mtb Ag tubes) did not differ significantly (0.00\u2009\u00b1\u20099.18 and 0.00\u2009\u00b1\u20094.25, respectively, IU\/ml;<jats:italic>p<\/jats:italic>\u00a0=\u00a00.58).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We demonstrated the potential of CD69 FC as a simple, rapid assay for clarifying indeterminate IGRA results and identifying active TB. With further improvements, CD69 FC may complement the IGRA to enhance TB risk stratification in the routine diagnostic workup.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cyto.b.22093","type":"journal-article","created":{"date-parts":[[2022,9,26]],"date-time":"2022-09-26T13:43:47Z","timestamp":1664199827000},"page":"471-486","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["<scp>CD69<\/scp>flow cytometry to complement interferon\u2010<i>\u03b3<\/i>release assay for active tuberculosis"],"prefix":"10.1002","volume":"102","author":[{"given":"Yoonjung","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, School of Medicine Kyungpook National University Daegu Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Man\u2010Hoon","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine Kyungpook National 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