Transcriptomics for child and adolescent tuberculosis.

Transcriptomics for child and adolescent tuberculosis.
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儿童和青少年结核病的转录组学。

DOI:
10.1111/imr.13116
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发表时间:
2022-08
影响因子:
8.7
通讯作者:
--
中科院分区:
医学1区
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--
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人类结核病(TB)是由结核分枝杆菌(Mtb)引起的。据估计,目前有7 000万儿童(<15岁)感染结核分枝杆菌,每年有120万儿童发展为结核病。其中,四分之一死亡。从结核分枝杆菌感染发展为疾病和从疾病发展为死亡的风险取决于多种病原体和宿主因素。年龄是所有这些转变的核心组成部分。儿童和青少年的结核病自然史与成人不同,这导致诊断、治疗和疫苗开发面临独特挑战。使用高通量方法(如微阵列分析或RNA测序)定量特定细胞或外周血中的RNA转录物,可以揭示感染和疾病期间宿主对Mtb的免疫反应,以及以无假设的方式了解治疗反应,疾病严重程度和疫苗接种。此外,基因表达谱可用于生物标志物发现,诊断疾病,预测未来疾病进展和监测对治疗的反应。在这里,我们回顾了转录组学在儿童和青少年中的作用,主要集中在血液中的工作,以了解疾病生物学,并区分疾病状态以协助临床决策。近年来,针对儿童和青少年的研究已经确定了具有诊断或预后潜力的血液基因表达标志物,这些标志物达到或超过了诊断工具的当前灵敏度和特异性目标。通过高通量方法鉴定的诊断和预后基因表达特征目前正在转化为诊断测试。
Tuberculosis (TB) in humans is caused by Mycobacterium tuberculosis (Mtb). It is estimated that 70 million children (<15 years) are currently infected with Mtb, with 1.2 million each year progressing to disease. Of these, a quarter die. The risk of progression from Mtb infection to disease and from disease to death is dependent on multiple pathogen and host factors. Age is a central component in all these transitions. The natural history of TB in children and adolescents is different to adults, leading to unique challenges in the development of diagnostics, therapeutics, and vaccines. The quantification of RNA transcripts in specific cells or in the peripheral blood, using high‐throughput methods, such as microarray analysis or RNA‐Sequencing, can shed light into the host immune response to Mtb during infection and disease, as well as understanding treatment response, disease severity, and vaccination, in a global hypothesis‐free manner. Additionally, gene expression profiling can be used for biomarker discovery, to diagnose disease, predict future disease progression and to monitor response to treatment. Here, we review the role of transcriptomics in children and adolescents, focused mainly on work done in blood, to understand disease biology, and to discriminate disease states to assist clinical decision‐making. In recent years, studies with a specific pediatric and adolescent focus have identified blood gene expression markers with diagnostic or prognostic potential that meet or exceed the current sensitivity and specificity targets for diagnostic tools. Diagnostic and prognostic gene expression signatures identified through high‐throughput methods are currently being translated into diagnostic tests.
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