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一种新型基于血液的结核病治疗监测检测方法。

A novel blood-based assay for treatment monitoring of tuberculosis.

机构信息

Departments of Medicine and of Epidemiology, Biostatistics & Occupational Health, McGill University, Montreal, Canada.

FIND, Chemin des Mines 9, Geneva, 1202, Switzerland.

出版信息

BMC Res Notes. 2021 Jun 30;14(1):247. doi: 10.1186/s13104-021-05663-z.

DOI:10.1186/s13104-021-05663-z
PMID:34193258
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8243580/
Abstract

OBJECTIVES

A novel 3-gene host transcriptional signature (GBP5, DUSP3 and KLF2) has been validated for tuberculosis (TB) treatment monitoring using laboratory-based RNA sequencing platforms. The signature was recently translated by Cepheid into a prototype cartridge-based test that can be run on the GeneXpert instrument. In this study, we prospectively evaluated the change in the expression of the cartridge-based 3-gene signature following treatment initiation among pulmonary TB patients who were microbiologically cured at the end of treatment.

RESULTS

The 3-gene signature expression level (TB score) changed significantly over time with respect to baseline among 31 pulmonary TB patients. The greatest increase in TB score occurred within the first month of treatment (median fold-increase in TB score: 1.08 [IQR 0.54-1.52]) and plateaued after 4 months of treatment (median TB score: 1.97 [IQR: 1.03-2.33]). The rapid and substantial increase of the TB score in the first month of treatment holds promise for the early identification of patients that respond to TB treatment. The plateau in TB score at 4 months may indicate early clearance of disease and could direct treatment to be shortened. These hypotheses need to be further explored with larger prospective treatment monitoring studies.

摘要

目的

使用基于实验室的 RNA 测序平台,验证了一种新的三基因宿主转录特征(GBP5、DUSP3 和 KLF2),用于监测结核病(TB)的治疗情况。该特征最近被 Cepheid 公司转化为一种基于试剂盒的原型检测方法,可在 GeneXpert 仪器上运行。在这项研究中,我们前瞻性评估了在治疗结束时微生物学治愈的肺结核患者在开始治疗后,基于试剂盒的三基因特征的表达变化。

结果

31 例肺结核患者的三基因特征表达水平(TB 评分)随时间相对于基线显著变化。TB 评分在治疗的第一个月内增加最多(TB 评分中位数增加倍数:1.08[IQR:0.54-1.52]),并在治疗 4 个月后趋于平稳(TB 评分中位数:1.97[IQR:1.03-2.33])。治疗第一个月 TB 评分的快速和显著增加有望早期识别对 TB 治疗有反应的患者。TB 评分在 4 个月时趋于平稳可能表明疾病早期清除,并可能指导缩短治疗时间。这些假设需要通过更大规模的前瞻性治疗监测研究进一步探索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03b2/8243580/d8e07af85667/13104_2021_5663_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03b2/8243580/d8e07af85667/13104_2021_5663_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03b2/8243580/d8e07af85667/13104_2021_5663_Fig1_HTML.jpg

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Sci Rep. 2020 May 25;10(1):8629. doi: 10.1038/s41598-020-65043-8.
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Concise whole blood transcriptional signatures for incipient tuberculosis: a systematic review and patient-level pooled meta-analysis.
口腔黏膜中发现的反映活动性肺结核的 DNA 甲基化特征在结核病治疗过程中发生变化。
Sci Rep. 2024 Nov 28;14(1):29552. doi: 10.1038/s41598-024-80570-4.
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Assessment of the Cepheid 3-gene Host Response Fingerstick Blood Test (MTB-HR) on rapid diagnosis of tuberculosis.评估赛沛 3 基因宿主反应指血检测(MTB-HR)对结核病的快速诊断。
Emerg Microbes Infect. 2023 Dec;12(2):2261561. doi: 10.1080/22221751.2023.2261561. Epub 2023 Oct 17.
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Gene signature discovery and systematic validation across diverse clinical cohorts for TB prognosis and response to treatment.针对结核病预后和治疗反应,在多个临床队列中进行基因特征发现和系统验证。
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J Infect. 2017 Dec;75(6):499-510. doi: 10.1016/j.jinf.2017.09.012. Epub 2017 Sep 20.
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