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 and Thoracic Tumor Research Institute, Beijing, People's Republic of China.
QJM. 2023 Dec 27;116(12):1002-1009. doi: 10.1093/qjmed/hcad214.
Interferon-γ release assays (IGRAs), which are widely used to diagnose tuberculosis (TB), cannot effectively discriminate latent TB infection (LTBI) from active TB (ATB). This study aimed to identify potential antigen-specific biomarkers for differentiating LTBI cases from ATB cases.
Ongoing recruitment was conducted of individuals meeting study inclusion criteria at Beijing Chest Hospital from May 2020 to April 2022; 208 participants were enrolled and assigned to three groups: HC (60 healthy controls), LTBI (52 subjects with LTBI) and ATB (96 ATB patients). After participants were assigned to the discovery cohort (20 or 21 subjects/group), all others were assigned to the verification cohort. Discovery cohort blood levels of 40 chemokines were measured using Luminex assays to identify chemokines that could be used to discriminate LTBI cases from ATB cases; candidate biomarkers were verified using enzyme-linked immunosorbent assay-based testing of validation cohort samples.
Luminex results revealed highest ATB group levels of numerous cytokines, growth factors and chemokines. Receiving operating characteristic curve-based analysis of 40 biomarkers revealed CCL8 (AUC = 0.890) and CXCL9 (AUC = 0.883) effectively discriminated between LTBI and TB cases; greatest diagnostic efficiency was obtained using both markers together (AUC = 0.929). Interpretation of CCL8 and CXCL9 levels for validation cohort IGRA-positive subjects (based on a 0.658-ng/ml cutoff) revealed ATB group CCL8-based sensitivity and specificity rates approaching 90.79% and 100.00%, respectively.
TB-specific chemokines hold promise as ATB diagnostic biomarkers. Additional laboratory confirmation is needed to establish whether CCL8-based assays can differentiate between ATB and LTBI cases, especially for bacteriologically unconfirmed TB cases.
干扰素-γ 释放试验（IGRAs）广泛用于诊断结核病（TB），但不能有效区分潜伏性 TB 感染（LTBI）与活动性 TB（ATB）。本研究旨在确定潜在的抗原特异性生物标志物，以区分 LTBI 病例和 ATB 病例。
本研究于 2020 年 5 月至 2022 年 4 月在北京胸科医院进行，符合纳入标准的患者被纳入研究并分为三组：健康对照组（HC，60 例健康对照）、LTBI 组（52 例 LTBI 患者）和 ATB 组（96 例 ATB 患者）。在将参与者分配到发现队列（每组 20 或 21 例）后，其余参与者被分配到验证队列。使用 Luminex 分析检测发现队列血液中的 40 种趋化因子水平，以确定可用于区分 LTBI 病例和 ATB 病例的趋化因子；使用验证队列样本的酶联免疫吸附试验验证候选生物标志物。
Luminex 结果显示，ATB 组多种细胞因子、生长因子和趋化因子水平最高。基于 40 种生物标志物的接收者操作特征曲线分析，CCL8（AUC=0.890）和 CXCL9（AUC=0.883）可有效区分 LTBI 和 TB 病例；同时使用两种标志物可获得最佳诊断效率（AUC=0.929）。根据 0.658-ng/ml 截断值，对验证队列 IGRA 阳性患者的 CCL8 和 CXCL9 水平进行解读，发现 ATB 组基于 CCL8 的敏感性和特异性率分别接近 90.79%和 100.00%。
TB 特异性趋化因子有望成为 ATB 诊断的生物标志物。需要进一步的实验室确认来确定基于 CCL8 的检测是否可以区分 ATB 和 LTBI 病例，特别是对于未经细菌学证实的 TB 病例。
