Consortium of Eosinophilic Gastrointestinal Disease Researchers

项目概要（总体） 这项更新申请旨在继续研究罕见的嗜酸性胃肠疾病，重点是 嗜酸性粒细胞性食管炎（EoE）、嗜酸性粒细胞性胃炎（EG）、嗜酸性粒细胞性胃肠炎（EGE）和嗜酸性粒细胞性 结肠炎（EC）通过嗜酸性胃肠疾病研究者联盟（CEGIR）。CEGIR将 促进高度协作、多中心、以患者为中心、转化和临床研究， 解决未满足的临床试验准备需求。CEGIR包括俄亥俄州的临床中心（协调中心）， 科罗拉多、阿肯色州、加州、伊利诺伊州、马里兰州、马萨诸塞州、明尼苏达州、纽约、北卡罗来纳州、 宾夕法尼亚州，田纳西州，德克萨斯州，和犹他州。CEGIR网站是根据其 在CEGIR的第一个周期之前和期间，彼此之间已有的合作和成功记录; 相关临床专业的多样化专业知识，包括胃肠病学，过敏，免疫学，营养学， 病理学;将儿科和成人患者整合到一个共同财团中的能力;良好的记录 卓越的临床和转化研究，涉及这一患者群体;和优秀的导师 影响早期学员职业发展的经验和能力。CEGIR站点已证明可访问 足够数量的EoE、EG、EGE和EC患者，如完成几项研究所证明的 包括这些患者的对照临床试验。积极主动的患者倡导团体（PAG），包括 美国嗜酸性粒细胞疾病伙伴关系和促进嗜酸性粒细胞疾病研究的运动， 在CEGIR的背景下协同合作。虽然还处于相对早期的阶段，CEGIR正在展示 通过调查人员之间的协作互动取得成功（在职业发展的各个阶段， 新成立的有前途的教师谁代表下一代的思想领袖），高度参与 PAG和合作机构，并已成为领先的研究小组，专注于罕见的EoE，EG， EGE和EC。目前和拟议的CEGIR计划正在为这组罕见的 疾病，例如建立准备参与的深度表型和基因型患者 在研究和新兴工具，量化临床状态，内窥镜异常，组织病理学， 病人的幸福。在这项更新申请中，研究人员计划研究一种已经开发的观察性方法， 队列患者，提供了一个有价值的机会进行纵向分析。这一队列的数据显示， 已经证实了2型过敏性免疫（如IL-13）在EG发病机制中的相关性， 本文所述的一项建议，以检查有希望的新的抗2型免疫的影响， 治疗（dupilumab，抗IL-4 Ra）。CEGIR包括转型试点可行性和职业提升 基于RDCRN内外协作的核心，将共同测试新的 假设，特别侧重于提高临床试验准备和吸引早期研究者 罕见疾病研究的职业。

Project Summary (Overall) This renewal application aims to continue research on rare eosinophilic gastrointestinal diseases with a focus on eosinophilic esophagitis (EoE), eosinophilic gastritis (EG), eosinophilic gastroenteritis (EGE), and eosinophilic colitis (EC) through the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR). CEGIR will promote highly collaborative, multi-site, patient-centric, translational, and clinical research with the intent of addressing unmet clinical trial readiness needs. CEGIR comprises clinical centers in Ohio (coordinating center), Colorado, Arkansas, California, Illinois, Maryland, Massachusetts, Minnesota, New York, North Carolina, Pennsylvania, Tennessee, Texas, and Utah. The CEGIR sites have been carefully chosen on the basis of their pre-existing record of collaboration and success with each other before and during the first cycle of CEGIR; diverse expertise in relevant clinical specialties including Gastroenterology, Allergy, Immunology, Nutrition, and Pathology; the ability to integrate pediatric and adult patients into a common consortium; well-established record of excellence in clinical and translational research involving this patient population; and excellent mentorship experience and capacity to impact early stage trainees’ career development. CEGIR sites have proven access to an adequate number of patients with EoE, EG, EGE, and EC, as evidenced from completion of several controlled clinical trials involving these patients. Proactive patient advocacy groups (PAGs), including the American Partnership for Eosinophilic Disorders and the Campaign Urging Research for Eosinophilic Disease, partner synergistically in the context of CEGIR. Though still in a relatively early stage, CEGIR is demonstrating success via its collaborative interactions between investigators (at all stages of career development including newly established promising faculty who represent the next generation of thought leaders), highly engaged PAGs, and partnering institutions and has emerged into the leading research group focused on rare EoE, EG, EGE, and EC. Current and proposed CEGIR initiatives are developing clinical trial readiness for this set of rare diseases, such as the establishment of deeply phenotyped and genotyped patients who are ready to participate in research and emerging tools that quantify clinical states, endoscopic abnormalities, tissue pathology, and patient well-being. In this renewal application, investigators plan to study an already developed observational cohort of patients, providing a valuable opportunity for longitudinal analyses. Data emerging from this cohort has already substantiated the association of type 2 allergic immunity (e.g. IL-13) in the pathogenesis of EG, leading to a proposal, described herein, to examine the impact of a promising new anti-type 2 immunity therapeutic (dupilumab, anti-IL-4Ra). CEGIR includes transformative Pilot-Feasibility and Career Enhancement Cores based on collaboration across and outside of the RDCRN and which will collectively test novel hypotheses, particularly focused on enhancing clinical trial readiness and attracting early stage investigators for careers in rare disease research.