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

摘要 上嗜酸性粒细胞性胃肠道疾病（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，包括嗜酸性粒细胞性胃炎EoG和嗜酸性粒细胞性十二指肠炎EoD）。 EGE是较罕见的EGID亚型之一，其导致所有性别和年龄的显著发病率。 EGE患者患有显著的胃肠道症状，经常被错误地标记为肠易激综合征， 腹痛和腹泻由于在确定足够的活检组织和嗜酸性粒细胞方面存在问题 由于活组织检查中的计数，这些疾病往往被低估，导致重大的医疗保健， 患者成本。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可能具有不同的 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浸润来反映。 疾病（EGE + EoE）或是否是孤立性嗜酸性粒细胞疾病（EGE）。我们建议调查 在伴有和不伴有EoE的EGE病例中的免疫学特征，并确定这些特征是否 预测未诊断为EGE的高危亲属胃肠道嗜酸性粒细胞计数升高。某些 基于组织的RNA特征（尤其是与嗜酸性粒细胞炎症相关的那些）可以准确地识别和 预测EGE，从而提供了一个解决方案，以认识不足，从穷人的活检协议和缺乏 嗜酸性粒细胞计数。我们最近发表的EoE增加了自我和家庭中的EGE风险。 鉴定具有Th2（或其他）介导的炎症的EoE先证者的亲属可能反映了增加的 嗜酸性粒细胞增多症，识别遗漏的疾病或将从嗜酸性粒细胞进一步检查中获益的患者 枚举本研究旨在通过对EGE的免疫病理学研究，进一步了解EGE的免疫病理学。 那些有和没有涉及EoE和相关条件。该项目将有助于识别 早期诊断和管理EGE的生物标志物，从而减少内镜检查和活检沿着 更加个性化的疾病管理。

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.