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基于全血 mRNA 表达的靶点以区分活动性结核病与潜伏感染和其他肺部疾病。

Whole blood mRNA expression-based targets to discriminate active tuberculosis from latent infection and other pulmonary diseases.

机构信息

Advanced Laboratory of Public Health (LASP), Gonçalo Moniz Institute (IGM) / Fiocruz, R. Waldemar Falcão, 121, Candeal, Salvador, BA, 40296-710, Brazil.

Molecular Oncology Research Center, Barretos Cancer Hospital, R. Antenor Duarte Villela, 1331, Dr. Paulo Prata, Barretos, SP, 14784-400, Brazil.

出版信息

Sci Rep. 2020 Dec 16;10(1):22072. doi: 10.1038/s41598-020-78793-2.

DOI:10.1038/s41598-020-78793-2
PMID:33328540
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7745039/
Abstract

Current diagnostic tests for tuberculosis (TB) are not able to predict reactivation disease progression from latent TB infection (LTBI). The main barrier to predicting reactivation disease is the lack of our understanding of host biomarkers associated with progression from latent infection to active disease. Here, we applied an immune-based gene expression profile by NanoString platform to identify whole blood markers that can distinguish active TB from other lung diseases (OPD), and that could be further evaluated as a reactivation TB predictor. Among 23 candidate genes that differentiated patients with active TB from those with OPD, nine genes (CD274, CEACAM1, CR1, FCGR1A/B, IFITM1, IRAK3, LILRA6, MAPK14, PDCD1LG2) demonstrated sensitivity and specificity of 100%. Seven genes (C1QB, C2, CCR2, CCRL2, LILRB4, MAPK14, MSR1) distinguished TB from LTBI with sensitivity and specificity between 82 and 100%. This study identified single gene candidates that distinguished TB from OPD and LTBI with high sensitivity and specificity (both > 82%), which may be further evaluated as diagnostic for disease and as predictive markers for reactivation TB.

摘要

目前的结核病（TB）诊断检测无法预测潜伏性 TB 感染（LTBI）向活动性疾病的进展。预测疾病再激活的主要障碍是缺乏对与潜伏感染向活动性疾病进展相关的宿主生物标志物的了解。在这里，我们应用基于免疫的 NanoString 平台基因表达谱来鉴定能够区分活动性 TB 与其他肺部疾病（OPD）的全血标志物，并可进一步评估作为 TB 再激活预测因子。在区分活动性 TB 患者和 OPD 患者的 23 个候选基因中，有 9 个基因（CD274、CEACAM1、CR1、FCGR1A/B、IFITM1、IRAK3、LILRA6、MAPK14、PDCD1LG2）的敏感性和特异性均为 100%。另外 7 个基因（C1QB、C2、CCR2、CCRL2、LILRB4、MAPK14、MSR1）则以 82%至 100%的敏感性和特异性将 TB 与 LTBI 区分开来。本研究鉴定出了具有高敏感性和特异性（均>82%）的可区分 TB 与 OPD 和 LTBI 的单一基因候选物，它们可进一步评估为疾病的诊断和 TB 再激活的预测标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/247f/7745039/12635d6daa17/41598_2020_78793_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/247f/7745039/bd04e59855f3/41598_2020_78793_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/247f/7745039/800e0d992417/41598_2020_78793_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/247f/7745039/12635d6daa17/41598_2020_78793_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/247f/7745039/bd04e59855f3/41598_2020_78793_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/247f/7745039/800e0d992417/41598_2020_78793_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/247f/7745039/12635d6daa17/41598_2020_78793_Fig3_HTML.jpg

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