U-BIOPRED研究中应用痰转录组甄别Th2和非Th2型哮喘
2017/11/20
摘要
哮喘的特性在于多样化的临床表型。我们的目标是通过104个中重度哮喘以及16个非哮喘患者的痰液细胞转录组来确定哮喘的分子表型。
关于508个对特定基因组分析的差异表达基因和变异基因组，在嗜伊红细胞和非嗜伊红细胞相关的痰炎症反应中过滤掉差异表达的基因之后，我们使用无偏倚的分级聚类。
我们定义了三个转录组相关的集群(TACs)：TAC1（特点是免疫受体IL33R，CCR3和TSLPR），TAC2（特点是干扰素，肿瘤坏死因子α和炎症相关的基因）和TAC3（特点是代谢通路的基因，泛素化和线粒体功能）。TAC1显示了最丰富的白介素-13/Th2和先天淋巴细胞2型的基因信号。TAC1的痰液嗜酸性粒细胞最多，呼出气一氧化氮最高，并且局限于口服皮质类固醇依赖性、频繁恶化以及严重气流阻塞的重症哮喘。TAC2显示痰嗜中性粒细胞，血清c反应蛋白水平和湿疹的患病率最高。TAC3有正常至中度高的痰嗜酸性粒细胞和FEV1维持良好。TAC1和TAC2的基因蛋白共同表达网络扩展了这个分子分类。
我们定义一个Th-2高的嗜酸性表型为TAC1，两个非Th2表型为TAC2和TAC3，它们的特点分别是炎症相关和代谢/线粒体通路。
T-helper cell type 2 (Th2) and non-Th2 molecular phenotypes of asthma using sputum transcriptomics in U-BIOPRED
Chih-Hsi Scott Kuo, Stelios Pavlidis, Matthew Loza, Fred Baribaud, Anthony Rowe, Iaonnis Pandis, Ana Sousa, Julie Corfield, Ratko Djukanovic, Rene Lutter, Peter J. Sterk, Charles Auffray, Yike Guo, Ian M. Adcock, Kian Fan Chung
European Respiratory Journal 2017 49: 1602135;
Abstract
Asthma is characterised by heterogeneous clinical phenotypes. Our objective was to determine molecular phenotypes of asthma by analysing sputum cell transcriptomics from 104 moderate-to-severe asthmatic subjects and 16 nonasthmatic subjects.
After filtering on the differentially expressed genes between eosinophil- and noneosinophil-associated sputum inflammation, we used unbiased hierarchical clustering on 508 differentially expressed genes and gene set variation analysis of specific gene sets.
We defined three transcriptome-associated clusters (TACs): TAC1 (characterised by immune receptors IL33R, CCR3 and TSLPR), TAC2 (characterised by interferon-, tumour necrosis factor-α- and inflammasome-associated genes) and TAC3 (characterised by genes of metabolic pathways, ubiquitination and mitochondrial function). TAC1 showed the highest enrichment of gene signatures for interleukin-13/T-helper cell type 2 (Th2) and innate lymphoid cell type 2. TAC1 had the highest sputum eosinophilia and exhaled nitric oxide fraction, and was restricted to severe asthma with oral corticosteroid dependency, frequent exacerbations and severe airflow obstruction. TAC2 showed the highest sputum neutrophilia, serum C-reactive protein levels and prevalence of eczema. TAC3 had normal to moderately high sputum eosinophils and better preserved forced expiratory volume in 1 s. Gene–protein coexpression networks from TAC1 and TAC2 extended this molecular classification.
We defined one Th2-high eosinophilic phenotype TAC1, and two non-Th2 phenotypes TAC2 and TAC3, characterised by inflammasome-associated and metabolic/mitochondrial pathways, respectively.
哮喘的特性在于多样化的临床表型。我们的目标是通过104个中重度哮喘以及16个非哮喘患者的痰液细胞转录组来确定哮喘的分子表型。
关于508个对特定基因组分析的差异表达基因和变异基因组，在嗜伊红细胞和非嗜伊红细胞相关的痰炎症反应中过滤掉差异表达的基因之后，我们使用无偏倚的分级聚类。
我们定义了三个转录组相关的集群(TACs)：TAC1（特点是免疫受体IL33R，CCR3和TSLPR），TAC2（特点是干扰素，肿瘤坏死因子α和炎症相关的基因）和TAC3（特点是代谢通路的基因，泛素化和线粒体功能）。TAC1显示了最丰富的白介素-13/Th2和先天淋巴细胞2型的基因信号。TAC1的痰液嗜酸性粒细胞最多，呼出气一氧化氮最高，并且局限于口服皮质类固醇依赖性、频繁恶化以及严重气流阻塞的重症哮喘。TAC2显示痰嗜中性粒细胞，血清c反应蛋白水平和湿疹的患病率最高。TAC3有正常至中度高的痰嗜酸性粒细胞和FEV1维持良好。TAC1和TAC2的基因蛋白共同表达网络扩展了这个分子分类。
我们定义一个Th-2高的嗜酸性表型为TAC1，两个非Th2表型为TAC2和TAC3，它们的特点分别是炎症相关和代谢/线粒体通路。
（复旦大学附属中山医院呼吸内科 李蕾 摘译 杨冬 审校）
（European Respiratory Journal 2017 49: 1602135）
（European Respiratory Journal 2017 49: 1602135）
T-helper cell type 2 (Th2) and non-Th2 molecular phenotypes of asthma using sputum transcriptomics in U-BIOPRED
Chih-Hsi Scott Kuo, Stelios Pavlidis, Matthew Loza, Fred Baribaud, Anthony Rowe, Iaonnis Pandis, Ana Sousa, Julie Corfield, Ratko Djukanovic, Rene Lutter, Peter J. Sterk, Charles Auffray, Yike Guo, Ian M. Adcock, Kian Fan Chung
European Respiratory Journal 2017 49: 1602135;
Abstract
Asthma is characterised by heterogeneous clinical phenotypes. Our objective was to determine molecular phenotypes of asthma by analysing sputum cell transcriptomics from 104 moderate-to-severe asthmatic subjects and 16 nonasthmatic subjects.
After filtering on the differentially expressed genes between eosinophil- and noneosinophil-associated sputum inflammation, we used unbiased hierarchical clustering on 508 differentially expressed genes and gene set variation analysis of specific gene sets.
We defined three transcriptome-associated clusters (TACs): TAC1 (characterised by immune receptors IL33R, CCR3 and TSLPR), TAC2 (characterised by interferon-, tumour necrosis factor-α- and inflammasome-associated genes) and TAC3 (characterised by genes of metabolic pathways, ubiquitination and mitochondrial function). TAC1 showed the highest enrichment of gene signatures for interleukin-13/T-helper cell type 2 (Th2) and innate lymphoid cell type 2. TAC1 had the highest sputum eosinophilia and exhaled nitric oxide fraction, and was restricted to severe asthma with oral corticosteroid dependency, frequent exacerbations and severe airflow obstruction. TAC2 showed the highest sputum neutrophilia, serum C-reactive protein levels and prevalence of eczema. TAC3 had normal to moderately high sputum eosinophils and better preserved forced expiratory volume in 1 s. Gene–protein coexpression networks from TAC1 and TAC2 extended this molecular classification.
We defined one Th2-high eosinophilic phenotype TAC1, and two non-Th2 phenotypes TAC2 and TAC3, characterised by inflammasome-associated and metabolic/mitochondrial pathways, respectively.
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根据吸烟状态，饮食质量和成人哮喘症状变化的一项纵向研究
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儿童胃食管反流患者的呼吸道症状
