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Systematic transethnic profiling of anticytokine and anti-leukocyte trafficking for the detection of drug-specific response signatures in the treatment of inflammatory bowel disease.

抗细胞因子和抗白细胞运输的系统性跨种族分析，用于检测炎症性肠病治疗中的药物特异性反应特征。

基本信息

批准号：
270655529
负责人：
Professor Dr. Stefan Schreiber
金额：
--
依托单位：
Institut für Klinische Molekularbiologie
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2015
资助国家：
德国
起止时间：
2014-12-31 至 2018-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/270655529?language=en
关键词：
Systematic transethnic profiling anticytokine anti

项目摘要

Inflammatory bowel disease (IBD) is a common, chronic, immune-mediated barrier disease. Current therapeutic interventions with anti-cytokine antibodies (TNF-a, IL-23/IL-12) reflect the intent to disrupt specific pathways of inflammatory immunopathology. Individual responses to biological treatment can thereby be exploited in a systems biology approach that employs a targeted mechanism of action (MOA) to decipher molecular signatures of therapeutic responses in the context of a distinct disease entity to describe common and unique transcriptional signatures of disease and drug-response. Using a translational approach (including whole exorne sequencing of DNA and whole transcriptome sequencing of RNA from peripheral blood mononuclear cells and mucosal biopsies, identifying drugspecific alterations of the gut microbiota before and at indicated time-points after drug administration) to investigateclinical and molecular phenotypes during therapeutic interference with cytokine signaling and leukocyte trafficking, we aim to trace common and unique signatures of drug- and therapy-specific responses. By comparing response signatures in a german and chinese population we aim to decipher genetic and environmental factors that influence individual drug- response in a diseased organ.

炎症性肠病（IBD）是一种常见的慢性免疫介导的屏障疾病。目前使用抗细胞因子抗体（TNF-α、IL-23/IL-12）的治疗性干预反映了破坏炎性免疫病理学的特定途径的意图。因此，可以在系统生物学方法中利用对生物治疗的个体反应，该方法采用靶向作用机制（MOA）来在不同疾病实体的背景下破译治疗反应的分子特征，以描述疾病和药物反应的共同和独特的转录特征。使用翻译方法（包括来自外周血单核细胞和粘膜活检的DNA的全exorne测序和RNA的全转录组测序，在给药前和给药后的指定时间点鉴定肠道微生物群的药物特异性改变）以研究在治疗干扰细胞因子信号传导和白细胞运输期间的临床和分子表型，我们的目标是追踪药物和治疗特异性反应的共同和独特特征。通过比较德国和中国人群的反应特征，我们的目标是破译影响患病器官中个体药物反应的遗传和环境因素。