Translational Research Unit, Department of Epidemiology and Preclinical Research, National Institute for Infectious Diseases "L. Spallanzani", Rome, Italy.
Department of Internal Medicine, National Taiwan University Hospital, Hsinchu, Taiwan.
Respirology. 2018 May;23(5):455-466. doi: 10.1111/resp.13272. Epub 2018 Feb 18.
Tuberculosis (TB) remains a devastating disease, yet despite its enormous toll on global health, tools to control TB are insufficient and often outdated. TB Biomarkers (TB-BM) would constitute extremely useful tools to measure infection status and predict outcome of infection, vaccination or therapy. There are several types of TB-BM: Correlate of Infection; Correlate of TB Disease; Correlate of Increased Risk of Developing Active TB Disease; Correlate of the Curative Response to Therapy; and Correlate of Protection (CoP). Most TB-BM currently studied are host-derived BM, and consist of transcriptomic, proteomic, metabolomic, cellular markers or marker combinations ('signatures'). In particular, vaccine-inducible CoP are expected to be transformative in developing new TB vaccines as they will de-risk vaccine research and development (R&D) as well as human testing at an early stage. In addition, CoP could also help minimizing the need for preclinical studies in experimental animals. Of key importance is that TB-BM are tested and validated in different well-characterized human TB cohorts, preferably with complementary profiles and geographically diverse populations: genetic and environmental factors such as (viral) coinfections, exposure to non-tuberculous mycobacteria, nutritional status, metabolic status, age (infants vs children vs adolescents vs adults) and other factors impact host immune set points and host responses across different populations. In this study, we review the most recent advances in research into TB-BM for the diagnosis of active TB, risk of TB development and treatment-induced TB cure.
结核病（TB）仍然是一种毁灭性疾病，尽管它对全球健康造成了巨大影响，但控制结核病的工具仍然不足且往往过时。结核病生物标志物（TB-BM）将成为衡量感染状况和预测感染、疫苗接种或治疗效果的极其有用的工具。TB-BM 有几种类型：感染相关生物标志物；结核病相关生物标志物；发生活动性结核病风险增加的相关生物标志物；治疗反应的相关生物标志物；和保护相关生物标志物（CoP）。目前研究最多的 TB-BM 是宿主来源的 BM，包括转录组、蛋白质组、代谢组、细胞标志物或标志物组合（“特征”）。特别是，疫苗诱导的 CoP 有望在开发新的结核病疫苗方面具有变革性，因为它们将降低疫苗研发（R&D）以及早期人体测试的风险。此外，CoP 还可以帮助减少在实验动物中进行临床前研究的需要。至关重要的是，TB-BM 在不同特征明确的人类结核病队列中进行测试和验证，最好具有互补的特征和地理上多样化的人群：遗传和环境因素，如（病毒）合并感染、接触非结核分枝杆菌、营养状况、代谢状况、年龄（婴儿与儿童与青少年与成人）和其他因素会影响不同人群的宿主免疫基准和宿主反应。在这项研究中，我们回顾了用于诊断活动性结核病、结核病发病风险和治疗诱导结核病治愈的 TB-BM 研究的最新进展。
