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使用蛋白质微阵列的新型血清生物标志物组合可区分活动性结核病与潜伏性结核感染。

Novel serological biomarker panel using protein microarray can distinguish active TB from latent TB infection.

作者信息

Li Jie, Wang Yaguo, Yan Liang, Zhang Chunlan, He Yanbin, Zou Jun, Zhou Yanhong, Zhong Cheng, Zhang Xueyu

机构信息

Department of Tuberculosis, Jiangxi Chest Hospital, Nanchang, 330006, China.

Key Laboratory of RNA Biology and National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.

出版信息

Microbes Infect. 2022 Nov-Dec;24(8):105002. doi: 10.1016/j.micinf.2022.105002. Epub 2022 May 20.

Abstract

BACKGROUND

Rapid laboratory technologies which can effectively distinguish active tuberculosis (ATB) from controls and latent tuberculosis infection (LTBI) are lacked.The objective of this study is to explore MTB biomarkers in serum that can distinguish ATB from LTBI.

METHODS

We constructed a tuberculosis protein microarray containing 64 MTB associated antigens. We then used this microarray to screen 180 serum samples, from patients with ATB and LTBI, and healthy volunteer controls. Both SAM (Significance analysis of microarrays) and ROC curve analysis were used to identify the differentially recognized biomarkers between groups. Extra 300 serum samples from patients with ATB and LTBI, and healthy volunteer controls were employed to validate the identified biomarkers using ELISA-based method.

RESULTS

According to the results, the best biomarker combinations of 4 proteins (Rv1860, RV3881c, Rv2031c and Rv3803c) were selected. The biomarker panel containing these 4 proteins has reached a sensitivity of 93.3% and specificity of 97.7% for distinguishing ATB from LTBI, and a sensitivity of 86% and specificity of 97.6% for distinguishing ATB from HC.

CONCLUSION

The biomarker combination in this study has high sensitivity and specificity in distinguishing ATB from LTBI, suggesting it is worthy for further validation in more clinical samples.

摘要

背景

缺乏能够有效区分活动性结核病(ATB)与对照以及潜伏性结核感染(LTBI)的快速实验室技术。本研究的目的是探索血清中可区分ATB与LTBI的结核分枝杆菌(MTB)生物标志物。

方法

我们构建了一个包含64种MTB相关抗原的结核蛋白质微阵列。然后使用该微阵列筛选来自ATB患者、LTBI患者和健康志愿者对照的180份血清样本。采用SAM(微阵列显著性分析)和ROC曲线分析来识别组间差异识别的生物标志物。另外采用基于酶联免疫吸附测定(ELISA)的方法,利用来自ATB患者、LTBI患者和健康志愿者对照的300份血清样本对所识别的生物标志物进行验证。

结果

根据结果,选择了4种蛋白质(Rv1860、RV3881c、Rv2031c和Rv3803c)的最佳生物标志物组合。包含这4种蛋白质的生物标志物组在区分ATB与LTBI时灵敏度达到93.3%,特异性达到97.7%,在区分ATB与健康对照(HC)时灵敏度为86%,特异性为97.6%。

结论

本研究中的生物标志物组合在区分ATB与LTBI方面具有高灵敏度和特异性,表明其值得在更多临床样本中进一步验证。

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