3-Gene-TB-SCORE Accuracy for Tuberculosis Disease Diagnosis Is Not Affected by Immune-Mediated Inflammatory Disease Comorbidity

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a major global health threat. Approximately one-quarter of the world’s population has an Mtb-specific immune response and are classified as having tuberculosis infection (TBI), with a lifelong 5–10% risk of developing TB disease....

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Vydáno v:	International journal of molecular sciences Ročník 26; číslo 22; s. 10931
Hlavní autoři:	Petruccioli, Elisa, Alonzi, Tonino, Navarra, Assunta, Altera, Anna Maria Gerarda, Cuzzi, Gilda, Farroni, Chiara, Repele, Federica, Gualano, Gina, Lindestam Arlehamn, Cecilia S., Palmieri, Fabrizio, Salmi, Andrea, Vanini, Valentina, Goletti, Delia
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	Switzerland MDPI AG 12.11.2025
Témata:	Accuracy Adult Aged Analysis BCG BCG vaccines Biomarkers CD4-Positive T-Lymphocytes - immunology Comorbidity Development and progression Disease Diseases Female Genes Health aspects Humans Immune response Immunotherapy Inflammation - immunology Italy Lymphocytes Male Massachusetts Medical diagnosis Middle Aged Mycobacterium tuberculosis - immunology Prospective Studies Regression analysis Rheumatoid arthritis ROC Curve T cells Taiwan Tuberculosis Tuberculosis - diagnosis Tuberculosis - epidemiology Tuberculosis - genetics Tuberculosis - immunology Viral infections Young Adult Italy Massachusetts Taiwan RNA biomarkers tuberculosis diagnosis TB-SCORE TB signatures
ISSN:	1422-0067, 1661-6596, 1422-0067
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Abstract	Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a major global health threat. Approximately one-quarter of the world’s population has an Mtb-specific immune response and are classified as having tuberculosis infection (TBI), with a lifelong 5–10% 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’s 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 0.70–0.71). 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.
AbstractList	Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a major global health threat. Approximately one-quarter of the world's population has an Mtb-specific immune response and are classified as having tuberculosis infection (TBI), with a lifelong 5-10% 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's 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 0.70-0.71). 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.Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a major global health threat. Approximately one-quarter of the world's population has an Mtb-specific immune response and are classified as having tuberculosis infection (TBI), with a lifelong 5-10% 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's 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 0.70-0.71). 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. Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a major global health threat. Approximately one-quarter of the world’s population has an Mtb-specific immune response and are classified as having tuberculosis infection (TBI), with a lifelong 5–10% 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’s 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 0.70–0.71). TB-SCORE was unaffected by IMID status or timing of Mtb exposure. Mtb-specific CD4[sup.+] 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. Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a major global health threat. Approximately one-quarter of the world’s population has an Mtb-specific immune response and are classified as having tuberculosis infection (TBI), with a lifelong 5–10% 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’s 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 0.70–0.71). 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. Tuberculosis (TB), caused by (Mtb), remains a major global health threat. Approximately one-quarter of the world's population has an Mtb-specific immune response and are classified as having tuberculosis infection (TBI), with a lifelong 5-10% 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's 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 0.70-0.71). 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.
Audience	Academic
Author	Repele, Federica Salmi, Andrea Altera, Anna Maria Gerarda Petruccioli, Elisa Farroni, Chiara Alonzi, Tonino Palmieri, Fabrizio Navarra, Assunta Vanini, Valentina Gualano, Gina Goletti, Delia Lindestam Arlehamn, Cecilia S. Cuzzi, Gilda
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Snippet	Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a major global health threat. Approximately one-quarter of the world’s population has an... Tuberculosis (TB), caused by (Mtb), remains a major global health threat. Approximately one-quarter of the world's population has an Mtb-specific immune... Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a major global health threat. Approximately one-quarter of the world's population has an...
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SubjectTerms	Accuracy Adult Aged Analysis BCG BCG vaccines Biomarkers CD4-Positive T-Lymphocytes - immunology Comorbidity Development and progression Disease Diseases Female Genes Health aspects Humans Immune response Immunotherapy Inflammation - immunology Italy Lymphocytes Male Massachusetts Medical diagnosis Middle Aged Mycobacterium tuberculosis - immunology Prospective Studies Regression analysis Rheumatoid arthritis ROC Curve T cells Taiwan Tuberculosis Tuberculosis - diagnosis Tuberculosis - epidemiology Tuberculosis - genetics Tuberculosis - immunology Viral infections Young Adult
Title	3-Gene-TB-SCORE Accuracy for Tuberculosis Disease Diagnosis Is Not Affected by Immune-Mediated Inflammatory Disease Comorbidity
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