Relationship of Immune Responses to Clinical Phenotype and Familial Risk in Eosinophilic Gastroenteritis

嗜酸性粒细胞性胃肠炎免疫反应与临床表型和家族风险的关系

基本信息

批准号：
10739453
负责人：
Kristina Lisa Allen-Brady
金额：
$ 23.1万
依托单位：
UNIVERSITY OF UTAH
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-08-15 至 2025-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10739453
关键词：
Abdomen Abdominal Pain Age Asthma Biological Markers Biopsy CCL17 gene CCL26 gene Chronic Comprehension Data Databases Development Diagnosis Diagnostic Diarrhea Diffuse Disease Disease Marker Dyspepsia Early Diagnosis Eczema Endoscopy Eosinophilia Eosinophilic Esophagitis Eosinophilic Gastritis Eosinophilic Gastrointestinal Disease Eosinophilic Infiltrate Etiology Family Family history of Family member First Degree Relative Gastrointestinal tract structure Gender Genealogy Genetic Transcription Healthcare Immune Immune response Immune signaling Immunologic Markers Immunologics Infiltration Inflammation Interleukin-5 Intestines Irritable Bowel Syndrome Link Mediating Medical Care Costs Medical Records Morbidity - disease rate Onset of illness Pathologic Patients Phenotype Population Database Protocols documentation Public Health Publishing RNA Race Relative Risks Risk Risk Factors Second Degree Relative Stomach Symptoms TSLP gene Tissues Up-Regulation Utah Work age group biomarker identification clinical phenotype comorbidity cost disease diagnosis disease phenotype disorder subtype duodenitis empowerment eosinophil eosinophilic gastroenteritis gastrointestinal high risk immunopathology improved medical complication molecular phenotype patient subsets personalized management predictive signature proband therapeutically effective transcriptome sequencing

项目摘要

ABSTRACT Upper Eosinophilic Gastrointestinal Diseases (EGIDs) include Eosinophilic Esophagitis (EoE) and Eosinophilic Gastroenteritis (EGE, which encompasses Eosinophilic Gastritis, EoG, and Eosinophilic Duodenitis, EoD). EGE is one of the more rare EGID subtypes which results in significant morbidity in all genders and ages. Patients with EGE suffer from significant GI symptoms, often mislabeled as irritable bowel syndrome, abdominal pain, and diarrhea. Due to issues in ascertainment of adequate biopsy tissues and eosinophil enumeration in biopsies, these diseases often go under-recognized, resulting in significant healthcare and patient cost. While the etiology of EGE is unknown, we and others have observed that 60-80% of EGE cases coexist with EoE and the remaining 20-40% are isolated EGE cases. Similar to EoE, EGE likely has different immune underpinnings potentially reflected by whether the disease manifests as a more diffuse eosinophilic disease (EGE+EoE) or whether it is isolated eosinophilic disease (EGE). We propose to investigate immunologic signatures in EGE cases with and without concurrent EoE and determine if these signatures predict elevated gastrointestinal eosinophil counts in high-risk relatives without a diagnosis of EGE. Certain tissue-based RNA signatures (especially those related to eosinophil inflammation) may accurately identify and predict EGE, and thus provide a solution to the under-recognition from poor biopsy protocols and lack of eosinophil enumeration. We have recently published that EoE increases one’s risk for EGE in self and families. Identification of relatives of EoE probands with Th2 (or other) mediated inflammation may reflect increased eosinophilia, identifying missed disease or those who would benefit from further work up with eosinophil enumeration. This proposal seeks to further understanding of the immunopathology of EGE through study of those with and without involvement of EoE and associated conditions. This project will aid in the identification of biomarkers for earlier diagnosis and management of EGE leading to fewer endoscopies and biopsies along with more personalized disease management.

抽象的上嗜酸性粒细胞胃肠道疾病 (EGID) 包括嗜酸性粒细胞性食管炎 (EoE) 和嗜酸性粒细胞性食管炎 (EoE) 胃肠炎（EGE，包括嗜酸性胃炎，EoG 和嗜酸性十二指肠炎，EoD）。 EGE 是较罕见的 EGID 亚型之一，导致所有性别和年龄的患者都有显着的发病率。 EGE 患者患有明显的胃肠道症状，通常被误认为是肠易激综合征，腹痛和腹泻是由于确定足够的活检组织和嗜酸性粒细胞的问题。由于活组织检查中的计数，这些疾病常常未被充分认识，从而导致重大的医疗保健和虽然 EGE 的病因尚不清楚，但我们和其他人观察到 60-80% 的 EGE 病例。与 EoE 共存，其余 20-40% 是孤立的 EGE 病例，与 EoE 类似，EGE 可能有不同的情况。免疫基础可能通过疾病是否表现为更弥漫的嗜酸性粒细胞来反映疾病（EGE+EoE）或是否为孤立性嗜酸性粒细胞疾病（EGE）。存在和不存在并发 EoE 的 EGE 病例中的免疫学特征，并确定这些特征是否预测未诊断 EGE 的高危亲属胃肠道嗜酸性粒细胞计数升高。基于组织的 RNA 特征（尤其是与嗜酸性粒细胞炎症相关的特征）可以准确识别和预测 EGE，从而为因活检方案不佳和缺乏识别而导致的识别不足问题提供解决方案我们最近发表了 EoE 会增加个人和家庭患 EGE 的风险。鉴定 EoE 先证者亲属是否患有 Th2（或其他）介导的炎症可能反映了炎症增加嗜酸粒细胞增多症，识别漏诊的疾病或那些将从嗜酸粒细胞增多症的进一步检查中受益的人该提案旨在通过研究进一步了解 EGE 的免疫病理学。那些有或没有参与 EoE 和相关条件的人，该项目将有助于识别。用于早期诊断和管理 EGE 的生物标志物，从而减少内窥镜检查和活检更加个性化的疾病管理。