新功能、新界面、新体验,扫描即可下载生物谷APP!
首页 » 体外诊断 » Lancet Respir Med:简单的血液测试准确诊断活动性肺结核

Lancet Respir Med:简单的血液测试准确诊断活动性肺结核

来源:生物谷 2016-02-22 11:51

2016年2月22日/生物谷BIOON/--一种简单的能够准确地诊断活动性肺结核(active tuberculosis)的血液测试可能使得控制这种疾病更加容易和低廉。结核病是由结核杆菌感染导致的。

在一项新的研究中,来自美国斯坦福大学医学院的研究人员鉴定出一种能够将活动性肺结核病人与潜伏性肺结核(latent tuberculosis)病人和其他疾病病人区分开来的基因表达特征。这种技术满足了世界卫生组织2014年呼吁科学家们开发出更好地诊断活动性肺结核病方法的需求。相关研究结果于2016年2月19日在线发表在Lancet Respiratory Medicine期刊上,论文标题为“Genome-wide expression for diagnosis of pulmonary tuberculosis: a multicohort analysis”。

在全球范围内,每年新增960万肺结核(tuberculosis, TB)病人,并且这种疾病每年杀死150万人。然而,这种疾病仍然难以诊断。论文通信作者和医学助理教授Purvesh Khatri博士说,“世界三分之一的人口目前感染上结核杆菌。即便他们当中只有10%的人患上活动性肺结核,那仍然占世界人口的3%,即2.4亿人。”

传统的诊断方法,如皮肤点刺试验和干扰素测定,不能将活动性肺结核病人与不再患病的病人或者仅仅是接种了肺结核疫苗的人区分开来。大多数国家给每个人接种肺结核疫苗。这些传统诊断方法也会漏掉HIV病人患有的肺结核。

一种高灵敏度的测试方法

常见的肺结核测试方法是检测病人咳出的痰液样本中这种导致疾病的结核杆菌。但是,作为论文第一作者的助理研究员Tim Sweeney博士说,病人有时很难产生所需的痰液。他说,“如果有人不能产生足够的痰液,或者如果你有一个不能遵照指令的小孩”,那么很难对他们进行诊断。痰液测试在监控病人如何对治疗作出反应方面几乎是无用的。当病人病情开始更好时,他们也不会产生用于这种测试的痰液。

这种由Khatri实验室开发的新测试方法以常见的血液作为测试样本,因而不需要收集痰液。它能够指示结核杆菌感染,即便病人感染上HIV,也是如此。不过,如果病人只是患上潜伏性肺结核或者之前已接种过肺结核疫苗,那么这种方法不会给出阳性结果。对这种方法而言,至于是哪种结核杆菌菌株感染病人,或者这种菌株是否对抗生素药物产生耐药性,都并不重要。它适合用于成人和儿童检测。

世界卫生组织要求开发一种在小孩患有活动性肺结核的至少66%的时间内检测时会给出阳性结果的测试方法。就儿童而言,这种Khatri测试方法的灵敏度是86%。如果这种测试结果是阴性的话,那么它的准确性是99%。也就是说,Khatri测试结果为阴性的100名病人当中,99人没有患上活动性肺结核。

这种测试方法的条件需求足够简单以至于它很可能能够在农村和不发达地区相对简单的现场条件下开展。任何一家医院都应该能够开展这种测试。没有电的乡村也可能使用常见的血液样本和一台太阳能供电的PCR仪(能够扩增DNA链)来准确地检测活动性肺结核病人。

链式反应

当这种病原菌感染人体细胞时,这种感染引发改变上百个基因表达的链式反应。Khatris团队鉴定出三个人基因:GBP5、DUSP3和KLF2,这三个基因的表达以一种一致性的方式发生变化,从而揭示出一种活动性肺结核感染的存在。

Khatris团队在来自11个不同数据集的1400份人样品中对这种三基因测试方法进行验证,结果证实了这种测试方法的诊断价值。

这种新的测试方法不仅准确地区分活动性肺结核病人,它也能够被用来监控病人以便观察他们对不同的疗法如何作出更好的反应。因此,它不仅能够被用来诊断和给出治疗意见,也能够被用来研究不同疗法的有效性。Khatri说,这种测试方法极高准确的阴性检测结果特别有助于在临床试验期间监控不同疗法的有效性。(生物谷 Bioon.com)

本文系生物谷原创编译整理,欢迎转载!点击 获取授权 。更多资讯请下载生物谷APP

doi:10.1016/S2213-2600(16)00048-5

Genome-wide expression for diagnosis of pulmonary tuberculosis: a multicohort analysis

Timothy E Sweeney, MD, Lindsay Braviak, Cristina M Tato, PhD, Dr Purvesh Khatri

Background
Active pulmonary tuberculosis is difficult to diagnose and treatment response is difficult to effectively monitor. A WHO consensus statement has called for new non-sputum diagnostics. The aim of this study was to use an integrated multicohort analysis of samples from publically available datasets to derive a diagnostic gene set in the peripheral blood of patients with active tuberculosis.

Methods
We searched two public gene expression microarray repositories and retained datasets that examined clinical cohorts of active pulmonary tuberculosis infection in whole blood. We compared gene expression in patients with either latent tuberculosis or other diseases versus patients with active tuberculosis using our validated multicohort analysis framework. Three datasets were used as discovery datasets and meta-analytical methods were used to assess gene effects in these cohorts. We then validated the diagnostic capacity of the three gene set in the remaining 11 datasets.

Findings
A total of 14 datasets containing 2572 samples from 10 countries from both adult and paediatric patients were included in the analysis. Of these, three datasets (N=1023) were used to discover a set of three genes (GBP5, DUSP3, and KLF2) that are highly diagnostic for active tuberculosis. We validated the diagnostic power of the three gene set to separate active tuberculosis from healthy controls (global area under the ROC curve (AUC) 0·90 [95% CI 0·85–0·95]), latent tuberculosis (0·88 [0·84–0·92]), and other diseases (0·84 [0·80–0·95]) in eight independent datasets composed of both children and adults from ten countries. Expression of the three-gene set was not confounded by HIV infection status, bacterial drug resistance, or BCG vaccination. Furthermore, in four additional cohorts, we showed that the tuberculosis score declined during treatment of patients with active tuberculosis.

Interpretation
Overall, our integrated multicohort analysis yielded a three-gene set in whole blood that is robustly diagnostic for active tuberculosis, that was validated in multiple independent cohorts, and that has potential clinical application for diagnosis and monitoring treatment response. Prospective laboratory validation will be required before it can be used in a clinical setting.

Funding
National Institute of Allergy and Infectious Diseases, National Library of Medicine, the Stanford Child Health Research Institute, the Society for University Surgeons, and the Bill and Melinda Gates Foundation.

温馨提示:87%用户都在生物谷APP上阅读,扫描立刻下载! 天天精彩!


相关标签

最新会议 培训班 期刊库