新功能、新界面、新体验,扫描即可下载生物谷APP!
首页 » 生物标志物 » Lancet:血液测试可提前18个月预测患上肺结核风险

Lancet:血液测试可提前18个月预测患上肺结核风险

来源:生物谷 2016-03-25 11:18

2016年3月25日/生物谷BIOON/--1995年底世界卫生组织(WHO)将每年3月24日作为世界防治结核病日(World Tuberculosis Day),是为了纪念1882年德国微生物学家罗伯特·科霍向一群德国柏林医生发表他对结核病病原菌的发现。今年3月24日是第21个“世界防治结核病日”,今年的活动主题是“社会共同努力,消除结核危害”。

世界上三分之一的人口被认为感染上结核分枝杆菌(Mycobacterium tuberculosis,MTB),即导致肺结核(TB)的细菌,但是只有一小部分人会患上有症状的疾病。如今,在一项新的研究中,一个国际研究小组在潜伏性MTB感染的人血液中鉴定出生物标志物,从而可能给医生们提供一种长期梦寐以求的工具:一种预测哪些人有高风险患上活动性肺结核(active TB)的方法。如果在进一步的临床试验中得到验证的话,那么一种基于这些血液生物标志物的测试方法可能允许医生们靶向治疗高危人群,因而阻止他们患病。相关研究结果于2016年3月23日在线发表在The Lancet期刊上,论文标题为“A blood RNA signature for tuberculosis disease risk: a prospective cohort study”。

这些为期十年的研究工作是由来自开普敦大学南非肺结核疫苗项目(South African Tuberculosis Vaccine Initiative)和美国西雅图传染病研究中心的研究人员领导的。

这些生物标志物的鉴定可分为两个部分。在第一部分,研究人员两年内收集了南非6000多名感染上MTB但其他方面都健康的青少年志愿者的血液样品(即第一项研究)。分析这些样品揭示出基因表达谱在最终患上TB的志愿者和仍旧保持健康的志愿者之间存在差异。这种由一组16个基因组成的TB风险“特征”早在感染上MTB的志愿者患上活动性肺结核18个月前就可在血液样品中检测到。

在第二部分,研究人员在针对来自南非和赞比亚的4500多名志愿者的研究(即第二项研究)中证实了这种基因风险特征(genetic risk signature)的预测能力。在第二项研究中的志愿者是健康的,但是与最近确诊患上活动性肺结核的人一起生活。相比于第一项研究中的志愿者,第二项研究中的志愿者在年龄、健康状态、种族和接触局部常见性MTB菌株方面差异更加大。尽管存在这些差异,在第一项研究中发现的相同基因风险特征也在第二项研究期间最终患上活动性肺结核的人血液样品中检测到。(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

A blood RNA signature for tuberculosis disease risk: a prospective cohort study

doi:10.1016/S0140-6736(15)01316-1

Daniel E Zak, PhD*, Adam Penn-Nicholson, PhD*, Thomas J Scriba, PhD*, Ethan Thompson, PhD†, Sara Suliman, PhD†, Lynn M Amon, PhD, Hassan Mahomed, MD, Mzwandile Erasmus, BSc, Wendy Whatney, BScHons, Prof Gregory D Hussey, FFCH(SA), Deborah Abrahams, DipMT, Fazlin Kafaar, DipNur, Tony Hawkridge, FCPHM, Suzanne Verver, PhD, E Jane Hughes, BScHons, Martin Ota, MD, Jayne Sutherland, PhD, Rawleigh Howe, MD, Prof Hazel M Dockrell, PhD, Prof W Henry Boom, MD, Bonnie Thiel, MS, Prof Tom H M Ottenhoff, MD, Prof Harriet Mayanja-Kizza, MD, Amelia C Crampin, FFPHM, Katrina Downing, PhD, Mark Hatherill, MD, Joe Valvo, BS, Smitha Shankar, MS, Shreemanta K Parida, MD, Prof Stefan H E Kaufmann, PhD, Prof Gerhard Walzl, MD, Alan Aderem, PhD, Prof Willem A Hanekom, FCP[SA] for the ACS and GC6-74 cohort study groups‡

Background
Identification of blood biomarkers that prospectively predict progression of Mycobacterium tuberculosis infection to tuberculosis disease might lead to interventions that combat the tuberculosis epidemic. We aimed to assess whether global gene expression measured in whole blood of healthy people allowed identification of prospective signatures of risk of active tuberculosis disease.

Methods
In this prospective cohort study, we followed up healthy, South African adolescents aged 12–18 years from the adolescent cohort study (ACS) who were infected with M tuberculosis for 2 years. We collected blood samples from study participants every 6 months and monitored the adolescents for progression to tuberculosis disease. A prospective signature of risk was derived from whole blood RNA sequencing data by comparing participants who developed active tuberculosis disease (progressors) with those who remained healthy (matched controls). After adaptation to multiplex quantitative real-time PCR (qRT-PCR), the signature was used to predict tuberculosis disease in untouched adolescent samples and in samples from independent cohorts of South African and Gambian adult progressors and controls. Participants of the independent cohorts were household contacts of adults with active pulmonary tuberculosis disease.

Findings
Between July 6, 2005, and April 23, 2007, we enrolled 6363 participants from the ACS study and 4466 from independent South African and Gambian cohorts. 46 progressors and 107 matched controls were identified in the ACS cohort. A 16 gene signature of risk was identified. The signature predicted tuberculosis progression with a sensitivity of 66·1% (95% CI 63·2–68·9) and a specificity of 80·6% (79·2–82·0) in the 12 months preceding tuberculosis diagnosis. The risk signature was validated in an untouched group of adolescents (p=0·018 for RNA sequencing and p=0·0095 for qRT-PCR) and in the independent South African and Gambian cohorts (p values <0·0001 by qRT-PCR) with a sensitivity of 53·7% (42·6–64·3) and a specificity of 82·8% (76·7–86) in the 12 months preceding tuberculosis.

Interpretation
The whole blood tuberculosis risk signature prospectively identified people at risk of developing active tuberculosis, opening the possibility for targeted intervention to prevent the disease.

Funding
Bill & Melinda Gates Foundation, the National Institutes of Health, Aeras, the European Union, and the South African Medical Research Council.

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