Abstract
OBJECTIVE: This study aimed to conduct a combined detection of Mycobacterium tuberculosis (MTB) infection using the tuberculosis (TB)-specific cytokine interferon-γ (IFN-γ) and interleukin-2 (IL-2) release assays in hospitalized children and adolescents with TB, evaluate the clinical value of this technique in the diagnosis of active TB in children and adolescents, and to analyze the related influencing factors. METHOD: A retrospective study was conducted to collect data from suspected pediatric and adolescent TB patients hospitalized at Chengdu Public Health Clinical Medical Center between April 2022 and December 2024. The combined detection of MTB infection using IFN-γ and IL-2 release assays (referred to as "dual-factor detection of TB infection") was carried out. Microbiological or molecular biological test results of MTB were also obtained. A total of 904 patients diagnosed with TB and 176 non-TB patients were included in the analysis of the effectiveness of dual-factor TB infection testing and related influencing factors. RESULTS: The combined detection of IFN-γ and/or IL-2 demonstrated improved diagnostic performance for active tuberculosis (ATB), with a sensitivity of 91.04% and specificity of 65.34% (AUC = 0.782, 95% CI 0.745-0.818). While IFN-γ and IL-2 levels showed no significant differences between MTB-positive and MTB-negative subgroups within the TB cohort (IFN-γ: 365.52 vs. 382.11 pg/ml; IL-2: 241.56 vs. 213.12 pg/ml), both cytokines were markedly elevated in the TB group compared to non-TB controls (IFN-γ: 68.1 pg/ml; IL-2: 41.68 pg/ml). Age-related variations were observed in IFN-γ (P < 0.05) but not IL-2 concentrations. Untreated patients exhibited higher median levels of IFN-γ (397.9 vs. 306.0 pg/ml) and IL-2 (239.2 vs. 173.3 pg/ml) than treated individuals. Among 904 ATB cases, 8.96% (81/904) were false-negative for both cytokines. Multivariate analysis identified advanced age, retreatment TB, pleural effusion, and TST positivity as independent risk factors for dual-negative results (all P < 0.05). CONCLUSION: In pediatric and adolescent patients, the combined detection of IFN-γ and IL-2 exhibits high sensitivity and specificity in diagnosing ATB. The test is convenient, stable, and highly accurate, making it of great significance for the early diagnosis of TB and the evaluation of treatment effects. Age, a positive TST result, retreatment TB, and the presence of pleural effusion may all influence the results of IFN-γ and/or IL-2.