Combined Analysis of IFN-γ, IL-2, IL-5, IL-10, IL-1RA and MCP-1 in QFT Supernatant Is Useful for Distinguishing Active Tuberculosis from Latent Infection.
Combined Analysis of IFN-γ, IL-2, IL-5, IL-10, IL-1RA and MCP-1 in QFT Supernatant Is Useful for Distinguishing Active Tuberculosis from Latent Infection.
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DOI：
10.1371/journal.pone.0152483
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Ohta K
中科院分区：
文献类型：
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作者：
Suzukawa M;Akashi S;Nagai H;Nagase H;Nakamura H;Matsui H;Hebisawa A;Ohta K
QuantiFERON®-TB Gold In-Tube test（QFT）是一种干扰素-γ释放试验，用于诊断结核分枝杆菌，但其在区分活动性结核病和潜伏性感染方面的不准确性是一个主要问题。因此，需要一种简单而准确的工具来在日常临床环境中实现该目标。本研究旨在鉴定特异性区分活动性结核和潜伏性感染的候选细胞因子。我们的研究人群包括31例活动性结核（结核病）患者，29例潜伏性结核感染（LTBI）患者和10例健康对照者。我们测定了特异性抗原刺激的血液样品（TBAg）和阴性对照样品（Nil）的QFT上清液中的27种细胞因子。我们通过创建受试者工作特征（ROC）曲线并测量曲线下面积（AUC）来分析其特异性和敏感性。在TBAg-Nil上清液中，IL-10、IFN-γ、MCP-1和IL-1 RA显示出高AUC，分别为0.8120、0.7842、0.7419和0.7375。与单独的每种细胞因子相比，这前四种细胞因子的联合测定在诊断活动性TB中显示阳性率，并且GDA分析显示MCP-1和IL-5在区分活动性TB与LTBI中是有效的，Wilk λ = 0.718（p < 0.001）。此外，利用IL-2的独特特征，即其TBAg-Nil上清液水平在LTBI中高于活动性TB，IFN-γ和IL-2之间的差异显示出0.8910的大AUC。总之，除了IFN-γ，QFT上清液中的IL-2、IL-5、IL-10、IL-1 RA和MCP-1可能有助于区分活动性TB和LTBI。这些细胞因子也可能帮助我们了解活动性TB和LTBI之间的发病机制的差异。
The QuantiFERON®-TB Gold In-Tube test (QFT), an interferon-γ release assay, is used to diagnose Mycobacterium tuberculosis, but its inaccuracy in distinguishing active tuberculosis from latent infection is a major concern. There is thus a need for an easy and accurate tool for achieving that goal in daily clinical settings. This study aimed to identify candidate cytokines for specifically differentiating active tuberculosis from latent infection. Our study population consisted of 31 active TB (tuberculosis) patients, 29 LTBI (latent tuberculosis infection) patients and 10 healthy control subjects. We assayed for 27 cytokines in QFT supernatants of both specific antigen-stimulated blood samples (TBAg) and negative-control samples (Nil). We analyzed their specificities and sensitivities by creating receiver operating characteristic (ROC) curves and measuring the area under those curves (AUCs). In TBAg–Nil supernatants, IL-10, IFN-γ, MCP-1 and IL-1RA showed high AUCs of 0.8120, 0.7842, 0.7419 and 0.7375, respectively. Compared with each cytokine alone, combined assay for these top four cytokines showed positive rates in diagnosing active TB, and GDA analysis revealed that MCP-1 and IL-5 are potent in distinguishing active TB from LTBI, with Wilk’s lambda = 0.718 (p < 0.001). Furthermore, utilizing the unique characteristic of IL-2 that its TBAg–Nil supernatant levels are higher in LTBI compared to active TB, the difference between IFN-γ and IL-2 showed a large AUC of 0.8910. In summary, besides IFN-γ, IL-2, IL-5, IL-10, IL-1RA and MCP-1 in QFT supernatants may be useful for distinguishing active TB from LTBI. Those cytokines may also help us understand the difference in pathogenesis between active TB and LTBI.