The Institute of Clinical Research and Translational Medicine, Gansu Provincial Hospital, 204 Donggang West Road, Chengguan District, Lanzhou, 730000, China.
BMC Pulm Med. 2020 Sep 18;20(1):248. doi: 10.1186/s12890-020-01280-x.
One forth whole-world population is infected with Mycobacterium tuberculosis (Mtb), but 90% of them are asymptotic latent infection without any symptoms but positive result in IFN-γ release assay. There is lack of ideal strategy to distinguish active tuberculosis (TB) and latent tuberculosis infection (LTBI). Some scientist had focused on a set of cytokines as biomarkers besides interferon- gamma (IFN-γ) to distinguish active TB and LTBI, but with considerable variance of results. This meta-analysis aimed to evaluate the overall discriminative ability of potential immune molecules to distinguish active TB and LTBI.
PubMed, the Cochrane Library, and Web of Science databases were searched to identify studies assessing diagnostic roles of cytokines for distinguishing active TB and LTBI published up to August 2018. The quality of enrolled studies was assessed using Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). The pooled diagnostic sensitivity and specificity of each cytokine was calculated by using Meta-DiSc software. Area under the summary receiver operating characteristic curve (AUC) was used to summarize the overall diagnostic performance of each biomarker.
Fourteen studies with 982 subjects met the inclusion criteria, including 526 active TB and 456 LTBI patients. Pooled sensitivity, specificity and AUC for discriminating between active TB and LTBI were analyzed for IL-2 (0.87, 0.61 and 0.9093), IP-10 (0.77, 0.73 and 0.8609), IL-5 (0.64, 0.75 and 0.8533), IL-13 (0.75, 0.71 and 0.8491), IFN-γ (0.67, 0.75 and 0.8031), IL-10 (0.68, 0.74 and 0.7957) and TNF-α (0.67, 0.64 and 0.7783). The heterogeneous subgroup analysis showed that cytokine detection assays, TB incidence, and stimulator with Mtb antigens are main influence factors for their diagnostic performance.
The meta-analysis showed cytokine production could assist the distinction between active TB and LTBI, IL-2 with the highest overall accuracy. No single biomarker is likely to show sufficiently diagnostic performance due to limited sensitivity and specificity. Further prospective studies are needed to identify the optimal combination of biomarkers to enhanced diagnostic capacity in clinical practice.
全世界有四分之一的人口感染了结核分枝杆菌（Mtb），但其中 90%为无症状的潜伏性感染，仅 IFN-γ 释放试验呈阳性。目前缺乏区分活动性结核病（TB）和潜伏性结核感染（LTBI）的理想策略。一些科学家已经关注到干扰素-γ（IFN-γ）以外的一组细胞因子作为生物标志物来区分活动性 TB 和 LTBI，但结果存在相当大的差异。本荟萃分析旨在评估潜在免疫分子区分活动性 TB 和 LTBI 的总体诊断能力。
检索 PubMed、Cochrane 图书馆和 Web of Science 数据库，以确定截至 2018 年 8 月评估细胞因子在区分活动性 TB 和 LTBI 中的诊断作用的研究。使用 Quality Assessment of Diagnostic Accuracy Studies-2（QUADAS-2）评估纳入研究的质量。使用 Meta-DiSc 软件计算每种细胞因子的汇总诊断敏感性和特异性。汇总受试者工作特征曲线下面积（AUC）用于总结每种生物标志物的总体诊断性能。
纳入了 14 项研究，共 982 例患者，包括 526 例活动性 TB 和 456 例 LTBI 患者。分析了用于区分活动性 TB 和 LTBI 的 IL-2、IP-10、IL-5、IL-13、IFN-γ、IL-10 和 TNF-α 的汇总敏感性、特异性和 AUC。结果显示，IL-2（0.87、0.61 和 0.9093）、IP-10（0.77、0.73 和 0.8609）、IL-5（0.64、0.75 和 0.8533）、IL-13（0.75、0.71 和 0.8491）、IFN-γ（0.67、0.75 和 0.8031）、IL-10（0.68、0.74 和 0.7957）和 TNF-α（0.67、0.64 和 0.7783）的检测具有诊断价值。异质性亚组分析表明，细胞因子检测方法、TB 发病率和刺激物是否为 Mtb 抗原是影响其诊断性能的主要因素。
本荟萃分析表明细胞因子的产生有助于区分活动性 TB 和 LTBI，IL-2 的总体准确性最高。由于敏感性和特异性有限，没有单一的生物标志物具有足够的诊断性能。需要进一步的前瞻性研究来确定最佳的生物标志物组合，以提高临床实践中的诊断能力。
