Observational studyFrontiers in immunology2026
Age-dependent immune heterogeneity and the limited diagnostic utility of peripheral blood biomarkers in pediatric tuberculosis: a real-world cohort study with multidimensional model evaluation.
Observational study in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Pediatric tuberculosis (TB) remains a diagnostic challenge due to atypical presentations and low pathogen detection rates. Overlapping clinical features with Objective: To investigate age-dependent heterogeneity in immune-inflammatory profiles among children with tuberculosis (TB) and to evaluate the additive diagnostic value of peripheral blood biomarkers beyond age alone, while assessing the impact of Methods: This retrospective observational study enrolled 280 children aged 0-18 years (186 TB cases, 94 non-TB controls) admitted between January 2024 and December 2025. Peripheral lymphocyte subsets, routine blood parameters, and systemic inflammatory indices (NLR, PLR, SII, MLR, SIRI) were compared between groups. Logistic regression identified independent correlates. ROC analysis, calibration curves, decision curve analysis (DCA), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used to evaluate model performance. Age-stratified analysis (three strata: <5, 5-12, ≥12 years) was performed using ANCOVA with age as a covariate. Age × Group interaction analyses and 1:1 age-matched sensitivity analyses were conducted to formally test effect modification and exclude age confounding. Sensitivity analyses comparing bacteriologically confirmed versus clinically diagnosed cases and MP-only controls versus TB-MP co-infected cases were also performed. Results: Age was the sole variable independently associated with pediatric TB (adjusted OR = 1.118, 95% CI: 1.046-1.194, P = 0.001). TB patients exhibited significantly lower CD8 Conclusion: Age is the key variable associated with pediatric TB and demonstrates marked age-dependent immune-inflammatory heterogeneity. Peripheral blood immune biomarkers added modest diagnostic information beyond age alone, with statistically significant yet clinically modest improvements. The incremental value of CD8
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