The Transcriptional Signature of Active Tuberculosis Reflects Symptom Status in Extra-Pulmonary and Pulmonary Tuberculosis.
The Transcriptional Signature of Active Tuberculosis Reflects Symptom Status in Extra-Pulmonary and Pulmonary Tuberculosis.
复制标题
DOI：
10.1371/journal.pone.0162220
复制
发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
O'Garra A
中科院分区：
文献类型：
--
作者：
Blankley S;Graham CM;Turner J;Berry MP;Bloom CI;Xu Z;Pascual V;Banchereau J;Chaussabel D;Breen R;Santis G;Blankenship DM;Lipman M;O'Garra A
结核分枝杆菌感染是全世界感染性死亡的主要原因。为了更好地了解宿主免疫反应以及识别疾病的潜在生物标志物，已经进行了基因表达微阵列研究，以分析结核病（TB）患者的血液转录反应。迄今为止，这些研究大多集中在肺结核患者，肺外结核患者的基因表达谱尚未与肺结核或结节病患者的基因表达谱进行比较。招募了一组新的肺外TB和结节病患者，并使用各种转录组学方法将这些患者的转录应答与肺TB患者的转录应答进行比较，包括测试先前定义的活动性TB的380个基因元签名。在这个由肺结核和肺外结核组成的新数据集中，380元特征广泛区分了活动性结核和健康对照。与肺结核相比，来自该元标记的前15个基因对于区分肺外结核与健康对照具有较低的灵敏度。我们发现肺结核和肺外结核的血液转录反应是异质性的，并反映了疾病症状的程度。肺外结核的转录特征显示了反映症状状态的基因表达的异质性，而肺结核的特征是不同的，基于更高比例的有症状的个体。这些发现对于基于mRNA的TB诊断的合理设计和实施具有重要意义。
Mycobacterium tuberculosis infection is a leading cause of infectious death worldwide. Gene-expression microarray studies profiling the blood transcriptional response of tuberculosis (TB) patients have been undertaken in order to better understand the host immune response as well as to identify potential biomarkers of disease. To date most of these studies have focused on pulmonary TB patients with gene-expression profiles of extra-pulmonary TB patients yet to be compared to those of patients with pulmonary TB or sarcoidosis. A novel cohort of patients with extra-pulmonary TB and sarcoidosis was recruited and the transcriptional response of these patients compared to those with pulmonary TB using a variety of transcriptomic approaches including testing a previously defined 380 gene meta-signature of active TB. The 380 meta-signature broadly differentiated active TB from healthy controls in this new dataset consisting of pulmonary and extra-pulmonary TB. The top 15 genes from this meta-signature had a lower sensitivity for differentiating extra-pulmonary TB from healthy controls as compared to pulmonary TB. We found the blood transcriptional responses in pulmonary and extra-pulmonary TB to be heterogeneous and to reflect the extent of symptoms of disease. The transcriptional signature in extra-pulmonary TB demonstrated heterogeneity of gene expression reflective of symptom status, while the signature of pulmonary TB was distinct, based on a higher proportion of symptomatic individuals. These findings are of importance for the rational design and implementation of mRNA based TB diagnostics.
登录
查看更多内容
通过外周血单核细胞基因表达谱鉴定区分活动性结核病和潜伏感染的新型生物标志物
影响因子：
3.7
作者：
Lu C;Wu J;Wang H;Wang S;Diao N;Wang F;Gao Y;Chen J;Shao L;Weng X;Zhang Y;Zhang W
通讯作者：
Zhang W
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
10
作者：
Kruijshaar, M. E.;Abubakar, I.
通讯作者：
Abubakar, I.
补体 C1q 水平升高标志着人类结核病处于活动状态。
影响因子：
3.7
作者：
Cai Y;Yang Q;Tang Y;Zhang M;Liu H;Zhang G;Deng Q;Huang J;Gao Z;Zhou B;Feng CG;Chen X
通讯作者：
Chen X
影响因子：
3.7
作者：
Bloom CI;Graham CM;Berry MP;Rozakeas F;Redford PS;Wang Y;Xu Z;Wilkinson KA;Wilkinson RJ;Kendrick Y;Devouassoux G;Ferry T;Miyara M;Bouvry D;Valeyre D;Gorochov G;Blankenship D;Saadatian M;Vanhems P;Beynon H;Vancheeswaran R;Wickremasinghe M;Chaussabel D;Banchereau J;Pascual V;Ho LP;Lipman M;O'Garra A
通讯作者：
O'Garra A