ORIGINAL RESEARCH article
Front. Cell. Infect. Microbiol.
Sec. Bacteria and Host
Volume 15 - 2025 | doi: 10.3389/fcimb.2025.1635486
This article is part of the Research TopicFactors for the Progression from Latent Tuberculosis Infection to Tuberculosis Disease Volume IIView all articles
Predicting Tuberculosis Progression in School Contacts: Novel Host Biomarkers for Early Risk Assessment
Provisionally accepted
- 1Jiangsu Provincial Center for Disease Control And Prevention, Nanjing, China
- 2Southeast University, Nanjing, China
- 3Nanjing Municipal Center for Disease Control and Prevention, Nanjing, China
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The low positive predictive value of tuberculin skin tests and interferon-γ release assays often results in unnecessary prophylaxis. This study aimed to identify antigen-specific biomarkers with high accuracy for predicting progression to active tuberculosis (ATB). QuantiFERON supernatants from a school tuberculosis outbreak cohort were analyzed, tracking students over two years to identify ATB cases. We assessed 67 cytokines using the Luminex Multiplex Array kit and applied LASSO and multivariate logistic regression to select predictors. A nomogram was developed from the coefficients of top predictors. Model performance was evaluated by AUC, C-index, and AIC. The levels of FGFbasic, GM-CSF, MPIF-1/CCL23, as well as the combinations of ratios of FGFbasic/GM-CSF and FGFbasic/MPIF-1/CCL23 were significantly associated with the risk of ATB. AUC values for the prediction models based on individual cytokines ranged from 0.607 to 0.713, notably lower than those of the fixed models based on the logistic regression (0.932) and LASSO regression (0.939). The LASSO regression model exhibited the best predictive performance, with a higher sensitivity (0.858 vs. 0.818) and specificity (0.949 vs.0.923), lower AIC (36.323 vs. 38.232), and equivalent C-index (0.939) compared to the traditional logistic regression model. The biomarkers identified in this study offer valuable insights for developing a more precise tool to identify individuals at high risk for rapid progression to ATB disease, enabling targeted interventions. The combination of multiple immune indicators shows significant promise in improving diagnostic accuracy.
Keywords: quantiferon supernatants, Tuberculosis, biomarkers, progression, LASSO
Received: 26 May 2025; Accepted: 14 Aug 2025.
Copyright: © 2025 Lu, Tian, Lian, Wang, Ding, Pan, Lu, Zhu and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Peng Lu, Jiangsu Provincial Center for Disease Control And Prevention, Nanjing, China
Limei Zhu, Jiangsu Provincial Center for Disease Control And Prevention, Nanjing, China
Qiao Liu, Jiangsu Provincial Center for Disease Control And Prevention, Nanjing, China
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