Developmental Immunotherapeutics For Allergic Diseases A

嗜酸性粒细胞性胃肠道疾病（EGID）是一系列以胃肠道嗜酸性粒细胞炎症为特征的疾病。在过去的十年中，EGID的发病率有所增加。EGID包括嗜酸性粒细胞性胃肠炎（EG）和嗜酸性粒细胞性食管炎，通常与食物和吸入过敏原过敏有关。许多EGID患者有许多食物过敏，在一些患者中，基于氨基酸的元素饮食是有效的治疗方法。这表明EGID发病机制是由于食物过敏原驱动的嗜酸性粒细胞炎症。目前，我们对这些疾病的理解和有效治疗这些疾病的能力存在重大差距。为了解决治疗和发病机制问题，我们最近完成了奥马珠单抗（治疗性单克隆抗IgE）治疗嗜酸性粒细胞性胃肠炎的临床试验。本研究提出了两个主要问题：1。是在嗜酸性胃肠疾病中具有临床实用性的抗IgE治疗剂，2. EGID的嗜酸性粒细胞性炎症特征是IgE依赖性过程吗？ 研究的初步分析表明，奥马珠单抗在所有受试者中耐受良好。奥马珠单抗治疗可有效阻断EG患者的IgE，如过敏原驱动的嗜碱性粒细胞活化的100-1000倍变化和游离IgE降低所示。奥马珠单抗治疗导致外周血嗜酸性粒细胞和受试者显著下降？EG症状。目前的工作集中在分析肠道活检，以检查奥马珠单抗对嗜酸性粒细胞浸润的影响。

Eosinophilic gastrointestinal diseases (EGID) are a spectrum of diseases characterized by eosinophilic inflammation of the gastrointestinal tract. In the past decade, there has been a increase in the incidence of EGID. EGID, including eosinophilic gastroenteritis (EG) and eosinophilic esophagitis, are commonly associated with food and aeroallergen hypersensitivity. Many EGID patients have numerous food allergies, and in some patients an amino acid based elemental diet is an effective treatment. This suggests that EGID pathogenesis is due to food allergen driven eosinophilic inflammation. At present, there are major gaps in our understanding of, and ability to effectively treat these diseases. To address both treatment and pathogenesis questions, we have recently completed a clinical trial of omalizumab (therapeutic monoclonal anti-IgE) for eosinophilic gastroenteritis. This study asks two major questions: 1. are anti-IgE therapeutics of clinical utility in eosinophilic gastrointestinal diseases, 2. is the eosinophilic inflammation characteristic of EGID an IgE dependent process? Preliminary analysis of the study demonstrates that omalizumab was well tolerated by all subjects. Omalizumab treatment was effective in blocking IgE in EG patients as shown by a 100-1000 fold shift in allergen driven basophil activation and by reductions in free IgE. Omalizumab treatment caused a significant drop in peripheral blood eosinophilia and in subjects? EG symptoms. Current work is focused on analysis of gut biopsies to examine the effect of omalizumab on eosinophilic infiltration.