Transcriptional blood signatures distinguish pulmonary tuberculosis, pulmonary sarcoidosis, pneumonias and lung cancers.
Transcriptional blood signatures distinguish pulmonary tuberculosis, pulmonary sarcoidosis, pneumonias and lung cancers.
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DOI：
10.1371/journal.pone.0070630
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发表时间：
2013
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：
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
需要新的方法来确定肺疾病（包括结节病和结核病）免疫发病机制的潜在因素，以开发新的治疗方法和生物标志物。比较结核病与其他类似肺部疾病的血液转录反应将促进对疾病途径的了解，并有助于区分具有相似临床表现的疾病。通过比较肉芽肿性疾病、结节病和肺结核的血液转录反应，确定这些疾病和其他肺部疾病的免疫发病机制的潜在因素。我们比较了肺结节病、肺结核、社区获得性肺炎和原发性肺癌以及健康对照者治疗前后和纯化白细胞人群的全血全基因组转录谱。干扰素诱导的中性粒细胞驱动的血液转录特征在结节病和结核病中都存在，在结核病中具有更高的丰度和表达。结节病特征的异质性与疾病活动性显著相关。肺炎和肺癌的转录谱显示炎症转录物过丰富。治疗成功后，结核和肺炎患者的转录活性显著降低。然而，糖皮质激素反应性结节病患者的转录活性显著增加。144个血液转录本能够将结核病与其他肺部疾病和对照区分开来。结核病和结节病显示出相似的血液转录谱，以干扰素诱导的转录物为主，而肺炎和肺癌显示出不同的特征，以炎症基因为主。结核和结节病在转录活性程度、谱的异质性和对治疗的转录反应方面也存在显著差异。
New approaches to define factors underlying the immunopathogenesis of pulmonary diseases including sarcoidosis and tuberculosis are needed to develop new treatments and biomarkers. Comparing the blood transcriptional response of tuberculosis to other similar pulmonary diseases will advance knowledge of disease pathways and help distinguish diseases with similar clinical presentations. To determine the factors underlying the immunopathogenesis of the granulomatous diseases, sarcoidosis and tuberculosis, by comparing the blood transcriptional responses in these and other pulmonary diseases. We compared whole blood genome-wide transcriptional profiles in pulmonary sarcoidosis, pulmonary tuberculosis, to community acquired pneumonia and primary lung cancer and healthy controls, before and after treatment, and in purified leucocyte populations. An Interferon-inducible neutrophil-driven blood transcriptional signature was present in both sarcoidosis and tuberculosis, with a higher abundance and expression in tuberculosis. Heterogeneity of the sarcoidosis signature correlated significantly with disease activity. Transcriptional profiles in pneumonia and lung cancer revealed an over-abundance of inflammatory transcripts. After successful treatment the transcriptional activity in tuberculosis and pneumonia patients was significantly reduced. However the glucocorticoid-responsive sarcoidosis patients showed a significant increase in transcriptional activity. 144-blood transcripts were able to distinguish tuberculosis from other lung diseases and controls. Tuberculosis and sarcoidosis revealed similar blood transcriptional profiles, dominated by interferon-inducible transcripts, while pneumonia and lung cancer showed distinct signatures, dominated by inflammatory genes. There were also significant differences between tuberculosis and sarcoidosis in the degree of their transcriptional activity, the heterogeneity of their profiles and their transcriptional response to treatment.
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DOI：
10.1164/rccm.200912-1855oc
发表时间：
2010-06-15
影响因子：
24.7
作者：
Lockstone, Helen E.;Sanderson, Sharon;Ho, Ling-Pei
通讯作者：
Ho, Ling-Pei
影响因子：
64.8
作者：
通讯作者：
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影响因子：
29.7
作者：
Cooper AM
通讯作者：
Cooper AM
影响因子：
25.7
作者：
Hoffmann, RM;Jung, MC;Pape, GR
通讯作者：
Pape, GR
DOI：
10.1164/ajrccm.164.10.2104046
发表时间：
2001-11-15
影响因子：
24.7
作者：
Baughman, RP;Teirstein, AS;Cherniak, R
通讯作者：
Cherniak, R