Transcriptional signatures of human peripheral blood mononuclear cells can identify the risk of tuberculosis progression from latent infection among individuals with silicosis.
Transcriptional signatures of human peripheral blood mononuclear cells can identify the risk of tuberculosis progression from latent infection among individuals with silicosis.
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人外周血单核细胞的转录特征可以识别矽肺患者潜伏感染导致结核病进展的风险
DOI：
10.1080/22221751.2021.1915184
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发表时间：
2021-12
影响因子：
13.2
通讯作者：
Zhang WH
中科院分区：
文献类型：
--
作者：
Ruan QL;Yang QL;Gao YX;Wu J;Lin SR;Zhou JY;Shao LY;Wang S;Liu QQ;Gao Y;Jiang N;Zhang WH
宿主免疫因子在潜伏性结核感染（LTBI）向活动性结核（TB）疾病的发展过程中起重要作用。然而，在血液生物标志物中测量的整体基因表达是否允许识别结核病风险的前瞻性特征仍然未知。因此，我们旨在评估LTBI受试者的人外周血单个核细胞（PBMCs）转录组特征区分未来结核病进展者和非进展者的能力。在一项513例矽肺患者结核病预防治疗的随机临床试验中，我们从观察组的50例LTBI患者中随机收集PBMC样本，对其进行37个月的结核病进展监测。采用差异表达分析、基因本体论分析、京都基因和基因组百科全书途径分析和加权基因共表达网络分析，比较两名发展为活动性结核病（进展者）和四名匹配的健康个体（非进展者）之间结核病风险的前瞻性特征。20个结核病特异性差异表达基因，在结核病进展者中显著下调，被发现与干扰素- γ反应相关基因相关。因此，本研究中分析的PBMC转录组谱可能有助于识别矽肺患者中有进展为活动性结核病风险的LTBI个体，并可能为有针对性的干预预防疾病进展提供新的见解。临床试验注册www.clinicaltrials.gov （NCT02430259）
ABSTRACT Host immune factor plays an important role in the progression of latent tuberculosis infection (LTBI) to active tuberculosis (TB) disease. However, whether global gene expression measured in blood biomarkers allows the identification of prospective signatures for TB risk remains unknown. Hence, we aimed to assess the ability of the transcriptome signatures in the human peripheral blood mononuclear cells (PBMCs) of LTBI subjects to differentiate future TB progressors from non-progressors. In a randomized clinical trial of TB preventive treatment of 513 participants with silicosis, we randomly collected PBMC samples from 50 LTBI subjects in the observational group, which was monitored for TB disease progression for 37 months. The prospective signatures of TB risk between the two participants who developed active TB (progressors) and four matched individuals who remained healthy (non-progressors) were compared using differential expression analysis, Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes pathway analysis, and Weighted Gene Co-expression Network Analysis. The 20 TB-specific differentially expressed genes, which were significantly downregulated in TB progressors, were revealed to be associated with interferon-gamma response-related genes. Therefore, the PBMC transcriptome profiles analyzed in this study may help identify LTBI individuals who are at risk of progressing to active TB among silicosis patients and may provide new insights for targeted intervention to prevent disease progression. Clinical trial registration www.clinicaltrials.gov (NCT02430259)
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影响因子：
16.6
作者：
Singhania A;Verma R;Graham CM;Lee J;Tran T;Richardson M;Lecine P;Leissner P;Berry MPR;Wilkinson RJ;Kaiser K;Rodrigue M;Woltmann G;Haldar P;O'Garra A
通讯作者：
O'Garra A
影响因子：
56.3
作者：
Rangaka, Molebogeng X.;Wilkinson, Katalin A.;Glynn, Judith R.;Ling, Daphne;Menzies, Dick;Mwansa-Kambafwile, Judith;Fielding, Katherine;Wilkinson, Robert J.;Pai, Madhukar
通讯作者：
Pai, Madhukar
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
2.8
作者：
Stirling C;Andrews S;Croft T;Vickers J;Turner P;Robinson A
通讯作者：
Robinson A
影响因子：
4.4
作者：
Denisenko, Elena;Guler, Reto;Schmeier, Sebastian
通讯作者：
Schmeier, Sebastian