{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T13:00:49Z","timestamp":1784206849881,"version":"3.55.0"},"reference-count":48,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"crossref","award":["GR-2018\u201312367178"],"award-info":[{"award-number":["GR-2018\u201312367178"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a major global health threat. Approximately one-quarter of the world\u2019s population has an Mtb-specific immune response and are classified as having tuberculosis infection (TBI), with a lifelong 5\u201310% risk of developing TB disease. This risk is elevated in individuals with immune-mediated inflammatory diseases (IMID) undergoing immunosuppressive therapies. To evaluate the diagnostic accuracy of the 3-gene TB-SCORE for TB disease in individuals within the TB spectrum, including those with TBI-IMID in a low TB endemic country, we prospectively enrolled 104 individuals with TB, TBI, TBI-IMID, and healthy donors. The 3-gene TB-SCORE and Mtb-specific response were evaluated and correlated with the participant\u2019s clinical status. Patients with TB disease showed a significantly lower TB-SCORE compared to other cohorts. ROC analysis showed moderate diagnostic accuracy for TB disease (AUC 0.70\u20130.71). TB-SCORE was unaffected by IMID status or timing of Mtb exposure. Mtb-specific CD4+ T cells had no correlation to TB-SCORE. This is the first evaluation of TB-SCORE as a diagnostic tool for TB disease in a low-endemic setting. While further validation is needed, our findings support its potential as a biomarker for TB disease, even in complex clinical settings involving IMID.<\/jats:p>","DOI":"10.3390\/ijms262210931","type":"journal-article","created":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T06:55:04Z","timestamp":1762930504000},"page":"10931","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["3-Gene-TB-SCORE Accuracy for Tuberculosis Disease Diagnosis Is Not Affected by Immune-Mediated Inflammatory Disease Comorbidity"],"prefix":"10.3390","volume":"26","author":[{"given":"Elisa","family":"Petruccioli","sequence":"first","affiliation":[{"name":"Translational Research Unit, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, 00149 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tonino","family":"Alonzi","sequence":"additional","affiliation":[{"name":"Translational Research Unit, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, 00149 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3662-4312","authenticated-orcid":false,"given":"Assunta","family":"Navarra","sequence":"additional","affiliation":[{"name":"Epidemiology Unit, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, 00149 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Maria Gerarda","family":"Altera","sequence":"additional","affiliation":[{"name":"Translational Research Unit, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, 00149 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilda","family":"Cuzzi","sequence":"additional","affiliation":[{"name":"Translational Research Unit, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, 00149 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Farroni","sequence":"additional","affiliation":[{"name":"Translational Research Unit, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, 00149 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2780-4100","authenticated-orcid":false,"given":"Federica","family":"Repele","sequence":"additional","affiliation":[{"name":"Translational Research Unit, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, 00149 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gina","family":"Gualano","sequence":"additional","affiliation":[{"name":"Respiratory Infectious Diseases Unit, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, 00149 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7302-8002","authenticated-orcid":false,"given":"Cecilia S.","family":"Lindestam Arlehamn","sequence":"additional","affiliation":[{"name":"Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, CA 92037, USA"},{"name":"Center for Vaccine Research, Department of Infectious Disease Immunology, Statens Serum Institut, DK-2300 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8184-6291","authenticated-orcid":false,"given":"Fabrizio","family":"Palmieri","sequence":"additional","affiliation":[{"name":"Respiratory Infectious Diseases Unit, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, 00149 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Salmi","sequence":"additional","affiliation":[{"name":"Translational Research Unit, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, 00149 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Vanini","sequence":"additional","affiliation":[{"name":"Translational Research Unit, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, 00149 Rome, Italy"},{"name":"Unit\u00e0 Operativa Semplice (UOS) Professioni Sanitarie Tecniche, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, 00149 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8360-4376","authenticated-orcid":false,"given":"Delia","family":"Goletti","sequence":"additional","affiliation":[{"name":"Translational Research Unit, National Institute for Infectious Diseases Lazzaro Spallanzani-IRCCS, 00149 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,12]]},"reference":[{"key":"ref_1","unstructured":"WHO (2025, November 02). 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