Comella-Del-Barrio Patricia, Abellana Rosa, Villar-Hernández Raquel, Jean Coute Mariette Doresca, Sallés Mingels Beatriz, Canales Aliaga Lydia, Narcisse Margareth, Gautier Jacqueline, Ascaso Carlos, Latorre Irene, Dominguez Jose, Perez-Porcuna Tomas M
Research Institute Germans Trias i Pujol, CIBER Respiratory Diseases, Universitat Autònoma de Barcelona, Badalona, Spain.
Department of Basic Clinical Practice, Faculty of Medicine, University of Barcelona, Barcelona, Spain.
Front Microbiol. 2019 Aug 14;10:1855. doi: 10.3389/fmicb.2019.01855. eCollection 2019.
In recent years, pediatric research on tuberculosis (TB) has focused on addressing new biomarkers with the potential to be used as immunological non-sputum-based methods for the diagnosis of TB in children. The aim of this study was to characterize a set of cytokines and a series of individual factors (ferritin, 25-hydroxyvitamin D [25(OH)D], parasite infections, and nutritional status) to assess different patterns for discriminating between active TB and latent TB infection (LTBI) in children. The levels of 13 cytokines in QuantiFERON-TB Gold In-Tube (QFT-GIT) supernatants were analyzed in 166 children: 74 with active TB, 37 with LTBI, and 55 uninfected controls. All cytokines were quantified using Luminex or ELISA. Ferritin and 25(OH)D were also evaluated using CLIA, and Ig-G antibodies were detected with a commercial ELISA kit. The combination of IP-10, IFN-γ, ferritin, and 25(OH)D achieved the best diagnostic performance to discriminate between active TB and LTBI cases in children in relation to the area under receiver operating characteristic (ROC) curve 0.955 (confidence interval 95%: 0.91-1.00), achieving optimal sensitivity and specificity for the development of a new test (93.2 and 90.0%, respectively). Children with TB showed higher ferritin levels and an inverse correlation between 25(OH)D and IFN-γ levels. The model proposed includes a combination of biomarkers for discriminating between active TB and LTBI in children to improve the accuracy of TB diagnosis in children. This combination of biomarkers might have potential for identifying the onset of primary TB in children.
近年来，儿童结核病研究聚焦于寻找新的生物标志物，这些标志物有潜力作为基于免疫学而非痰液的方法用于儿童结核病诊断。本研究的目的是对一组细胞因子和一系列个体因素（铁蛋白、25-羟基维生素D [25(OH)D]、寄生虫感染和营养状况）进行特征分析，以评估区分儿童活动性结核病和潜伏性结核感染（LTBI）的不同模式。对166名儿童的全血γ干扰素释放试验（QFT-GIT）上清液中的13种细胞因子水平进行了分析：74名活动性结核病患儿、37名LTBI患儿和55名未感染对照。所有细胞因子均使用Luminex或酶联免疫吸附测定（ELISA）进行定量。铁蛋白和25(OH)D也使用化学发光免疫分析（CLIA）进行评估，Ig-G抗体用商用ELISA试剂盒检测。在受试者工作特征（ROC）曲线下面积方面，IP-10、干扰素-γ、铁蛋白和25(OH)D的组合在区分儿童活动性结核病和LTBI病例时表现出最佳诊断性能，曲线下面积为0.955（95%置信区间：0.91-1.00），为开发新检测方法实现了最佳敏感性和特异性（分别为93.2%和90.0%）。结核病患儿铁蛋白水平较高，25(OH)D与干扰素-γ水平呈负相关。所提出的模型包括用于区分儿童活动性结核病和LTBI的生物标志物组合，以提高儿童结核病诊断的准确性。这种生物标志物组合可能在识别儿童原发性结核病发病方面具有潜力。
