Chang Chunyan, Ma Zichun, Ren Weicong, Wang Wei, Liu Haohan, Zhong Rujie, Li Shanshan, Gao Mengqiu, Pang Yu
Department of Bacteriology and Immunology, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis and Thoracic Tumor Research Institute, Postal No 9, Beiguan Street, Tongzhou District, Beijing, 101149, People's Republic of China.
Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, People's Republic of China.
Infection. 2025 May 25. doi: 10.1007/s15010-025-02571-3.
Identifying recent tuberculosis (TB) infection individuals and administering TB preventive therapy (TPT) are critical strategies for controlling TB. However, current diagnostics fail to identify these individuals at high risk for developing active TB. Herein, we aimed to explore the candidate biomarkers to distinguish recent TB infection from remote TB infection individuals.
Close contacts of TB patients were continuously recruited. A total of 121 participants meeting study inclusion criteria were assigned to screening and validation cohorts, consisting of 45 participants assigned to screening cohort, and 76 participants assigned to validation cohort. The inflammation-related protein biomarkers in Mtb antigen-stimulated blood plasma were measured in the screening cohort using the Olink targeted proteomics. The candidate biomarkers were verified in validation cohort with the customized Luminex-based multiplex microbead array.
Quantitative proteomics analysis reveals that significant differences in Mycobacterium tuberculosis (Mtb) antigen-stimulated blood plasma levels of CCL3, CCL20, CCL23 and TNF-α between remote and recent TB infection group. The different response profiles of memory immune cells to Mtb antigens could stem from activation of the NF-κB signaling pathway. The levels of CCL3, CCL20 and TNF-α were predictive of recent TB infection group, of which CCL3 exhibited the best performance with an AUC value of 0.859, yielding a sensitivity and specificity of 86.4% and 75%, respectively.
The Mtb antigen-specific assay utilizing CCL3 exhibits superior diagnostic performance and could potentially enhance diagnostic accuracy for identifying recent TB infection patients among LTBI individuals.
识别近期结核（TB）感染个体并给予结核预防性治疗（TPT）是控制结核病的关键策略。然而，目前的诊断方法无法识别出这些有发展为活动性结核病高风险的个体。在此，我们旨在探索候选生物标志物，以区分近期结核感染个体与既往结核感染个体。
持续招募结核病患者的密切接触者。共有121名符合研究纳入标准的参与者被分配到筛查队列和验证队列，其中45名参与者被分配到筛查队列，76名参与者被分配到验证队列。在筛查队列中，使用Olink靶向蛋白质组学检测结核分枝杆菌（Mtb）抗原刺激血浆中的炎症相关蛋白质生物标志物。候选生物标志物在验证队列中用定制的基于Luminex的多重微珠阵列进行验证。
定量蛋白质组学分析显示，既往结核感染组与近期结核感染组在Mtb抗原刺激血浆中CCL3、CCL20、CCL23和TNF-α水平存在显著差异。记忆免疫细胞对Mtb抗原的不同反应谱可能源于NF-κB信号通路的激活。CCL3、CCL20和TNF-α水平可预测近期结核感染组，其中CCL3表现最佳，AUC值为0.859，敏感性和特异性分别为86.4%和75%。
利用CCL3的Mtb抗原特异性检测具有卓越的诊断性能，有可能提高在潜伏性结核感染个体中识别近期结核感染患者的诊断准确性。
