Novel eosinophilic gene expression networks associated with IgE in two distinct asthma populations.
Novel eosinophilic gene expression networks associated with IgE in two distinct asthma populations.
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DOI：
10.1111/cea.13249
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发表时间：
2018-12
期刊：
影响因子：
--
通讯作者：
Lasky-Su JA
中科院分区：
文献类型：
--
作者：
Virkud YV;Kelly RS;Croteau-Chonka DC;Celedón JC;Dahlin A;Avila L;Raby BA;Weiss ST;Lasky-Su JA
哮喘是一个重大的公共卫生负担;然而，靶向免疫球蛋白E（IgE）介导的途径的新型生物疗法拓宽了该疾病的临床治疗选择。在这项研究中，我们试图确定参与测定哮喘患者血清IgE水平的基因转录物和基因网络，这可以帮助开发新的治疗药物。我们分析了来自哥斯达黎加哮喘遗传学研究的326名6 - 12岁哥斯达黎加哮喘儿童和来自儿童哮喘管理项目试验的610名16 - 25岁哮喘青年的横断面研究的基因表达数据。我们利用差异基因表达分析，并对25，060个基因进行加权基因共表达网络分析，以确定与总IgE相关的基因转录本和网络模块，调整年龄和性别。我们使用途径富集分析来确定重要模块的关键生物途径。我们比较了两个群体之间重复的发现。我们确定了31种与总IgE相关的转录本，这些转录本在两个研究队列之间重复。这些结果对于增加的嗜酸性粒细胞相关转录物（包括IL 5 RA、CLC、SMPD 3、CCL 23、CEBPE）是显著的。途径富集鉴定了T细胞耐受性的调节在总IgE水平的测定中是重要的，支持IDO 1的关键作用。这些结果提供了强有力的证据表明，与总IgE水平相关的生物学意义的基因表达谱（特别是与嗜酸性粒细胞和调节性T细胞通路相关）可以在儿童期诊断为哮喘的个体中鉴定。这些谱及其组成基因可能代表新的治疗靶点。
Asthma represents a significant public health burden; however, novel biological therapies targeting immunoglobulin E (IgE)-mediated pathways have widened clinical treatment options for the disease. In this study we sought to identify gene transcripts and gene networks involved in the determination of serum IgE levels in people with asthma that can help inform the development of novel therapeutic agents. We analyzed gene expression data from a cross-sectional study of 326 Costa Rican children with asthma, aged 6 to 12 years, from the Genetics of Asthma in Costa Rica Study and 610 young adults with asthma, aged 16 to 25 years, from the Childhood Asthma Management Program trial. We utilized differential gene expression analysis and performed weighted gene co-expression network analysis on 25,060 genes, to identify gene transcripts and network modules associated with total IgE, adjusting for age and gender. We used pathway enrichment analyses to identify key biological pathways underlying significant modules. We compared findings that replicated between both populations. We identified 31 transcripts associated with total IgE that replicated between the two study cohorts. These results were notable for increased eosinophil-related transcripts (including IL5RA, CLC, SMPD3, CCL23, CEBPE). Pathway enrichment identified the regulation of T cell tolerance as important in the determination of total IgE levels, supporting a key role for IDO1. These results provide robust evidence that biologically meaningful gene expression profiles (relating to eosinophilic and regulatory T cell pathways in particular) associated with total IgE levels can be identified in individuals diagnosed with asthma during childhood. These profiles and their constituent genes may represent novel therapeutic targets.
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DOI：
10.1016/j.jaci.2011.09.029
发表时间：
2012-03
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Granada M;Wilk JB;Tuzova M;Strachan DP;Weidinger S;Albrecht E;Gieger C;Heinrich J;Himes BE;Hunninghake GM;Celedón JC;Weiss ST;Cruikshank WW;Farrer LA;Center DM;O'Connor GT
通讯作者：
O'Connor GT
影响因子：
14.2
作者：
Du, Rose;Litonjua, Augusto A.;Weiss, Scott T.
通讯作者：
Weiss, Scott T.
影响因子：
12.4
作者：
Devouassoux, G.;Pachot, A.;Pacheco, Y.
通讯作者：
Pacheco, Y.
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
2.7
作者：
Ago, Hideo;Okimoto, Noriaki;Miyano, Masashi
通讯作者：
Miyano, Masashi