结核特异性细胞因子IFN-γ和IL-2联合检测在儿童及青少年活动性肺结核诊断中的临床价值及影响因素分析

Analysis of the clinical value and influencing factors of combined detection of tuberculosis-specific cytokines IFN-γ and IL-2 in the diagnosis of active tuberculosis in children and adolescents.

作者信息

Chen Jinyu, Deng Bin, Li Maoying, Huang Yuhong, Han Jing, Li Qiong, Gao Li, Chen Lei, Tang Shenjie

机构信息

The Public Health Clinical Center of Chengdu, Chengdu, China.

Beijing Chest Hospital, Capital Medical University, Beijing, China.

出版信息

Eur J Med Res. 2025 Aug 11;30(1):732. doi: 10.1186/s40001-025-02895-8.

DOI:10.1186/s40001-025-02895-8

PMID:40790778

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.

摘要

目的

本研究旨在采用结核特异性细胞因子干扰素-γ（IFN-γ）和白细胞介素-2（IL-2）释放试验对住院的儿童和青少年结核病（TB）患者进行结核分枝杆菌（MTB）感染的联合检测，评估该技术在儿童和青少年活动性结核病诊断中的临床价值，并分析相关影响因素。

方法

进行一项回顾性研究，收集2022年4月至2024年12月在成都公共卫生临床医疗中心住院的疑似儿童和青少年结核病患者的数据。采用IFN-γ和IL-2释放试验联合检测MTB感染（称为“结核感染双因子检测”）。还获取了MTB的微生物学或分子生物学检测结果。共纳入904例确诊结核病患者和176例非结核病患者，分析结核感染双因子检测的有效性及相关影响因素。

结果

IFN-γ和/或IL-2的联合检测对活动性结核病（ATB）显示出更好的诊断性能，敏感性为91.04%，特异性为65.34%（AUC = 0.782，95%CI 0.745 - 0.818）。在结核病队列中，MTB阳性和MTB阴性亚组之间的IFN-γ和IL-2水平无显著差异（IFN-γ：365.52对382.11 pg/ml；IL-2：241.56对213.12 pg/ml），但与非结核病对照组相比，结核病组的两种细胞因子均显著升高（IFN-γ：68.1 pg/ml；IL-2：41.68 pg/ml）。IFN-γ浓度存在年龄相关差异（P < 0.05），而IL-2浓度无此差异。未治疗患者的IFN-γ（397.9对306.0 pg/ml）和IL-2（239.2对173.3 pg/ml）中位数水平高于治疗患者。在904例ATB病例中，8.96%（81/904）的两种细胞因子检测均为假阴性。多因素分析确定高龄、复治结核病、胸腔积液和结核菌素皮肤试验（TST）阳性为双阴性结果的独立危险因素（均P < 0.05）。