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血液基因表达特征对泰国活动性肺结核的诊断价值:一项初步研究。

Diagnostic value of blood gene expression signatures in active tuberculosis in Thais: a pilot study.

作者信息

Satproedprai N, Wichukchinda N, Suphankong S, Inunchot W, Kuntima T, Kumpeerasart S, Wattanapokayakit S, Nedsuwan S, Yanai H, Higuchi K, Harada N, Mahasirimongkol S

机构信息

Department of Medical Sciences, Medical Genetics Center, Medical Life Sciences Institute, Ministry of Public Health, Nonthaburi, Thailand.

TB/HIV Research Foundation, Chiangrai, Thailand.

出版信息

Genes Immun. 2015 Jun;16(4):253-60. doi: 10.1038/gene.2015.4. Epub 2015 Mar 12.

Abstract

Tuberculosis (TB) is a major global health problem. Routine laboratory tests or newly developed molecular detection are limited to the quality of sputum sample. Here we selected genes specific to TB by a minimum redundancy-maximum relevancy package using publicly available microarray data and determine level of selected genes in blood collected from a Thai TB cohort of 40 active TB patients, 38 healthy controls and 18 previous TB patients using quantitative real-time PCR. FCGR1A, FCGR1B variant 1, FCGR1B variant 2, APOL1, GBP5, PSTPIP2, STAT1, KCNJ15, MAFB and KAZN had significantly higher expression level in active TB individuals as compared with healthy controls and previous TB cases (P<0.01). A mathematical method was applied to calculate TB predictive score, which contains the level of expression of seven genes and this score can identify active TB cases with 82.5% sensitivity and 100% specificity as compared with conventional culture confirmation. In addition, TB predictive scores in active TB patients were reduced to normal after completion of standard short-course therapy, which was mostly in concordant with the disease outcome. These finding suggested that blood gene expression measurement and TB Sick Score could have potential value in terms of diagnosis of TB and anti-TB treatment monitoring.

摘要

结核病(TB)是一个重大的全球健康问题。常规实验室检测或新开发的分子检测都受限于痰液样本的质量。在此,我们使用公开可用的微阵列数据,通过最小冗余-最大相关性程序包选择结核病特异性基因,并使用定量实时聚合酶链反应确定从40名活动性结核病患者、38名健康对照和18名既往结核病患者组成的泰国结核病队列采集的血液中所选基因的水平。与健康对照和既往结核病病例相比,FCGR1A、FCGR1B变体1、FCGR1B变体2、APOL1、GBP5、PSTPIP2、STAT1、KCNJ15、MAFB和KAZN在活动性结核病个体中的表达水平显著更高(P<0.01)。应用一种数学方法计算结核病预测评分,该评分包含七个基因的表达水平,与传统培养确诊相比,该评分能够以82.5%的敏感性和100%的特异性识别活动性结核病病例。此外,活动性结核病患者完成标准短程治疗后,结核病预测评分降至正常,这与疾病转归基本一致。这些发现表明,血液基因表达检测和结核病患病评分在结核病诊断和抗结核治疗监测方面可能具有潜在价值。

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