Developmental Immunotherapeutics For Allergic Diseases A

嗜酸性胃肠道疾病(EGID)是以胃肠道嗜酸性炎症为特征的一系列疾病。在过去的十年中，EGID的发病率有所增加。EGID包括嗜酸性胃肠炎(EG)和嗜酸性食管炎，通常与食物和空气过敏原有关。许多EGID患者有许多食物过敏，在一些患者中，以氨基酸为基础的元素饮食是一种有效的治疗方法。这表明EGID的发病机制是由于食物过敏原引起的嗜酸性炎症。目前，我们对这些疾病的认识和有效治疗的能力存在重大差距。为了解决治疗和发病机制问题，我们最近完成了一项治疗嗜酸性胃肠炎的奥马珠单抗(治疗性单抗IgE)的临床试验。这项研究提出了两个主要问题：1.抗IgE疗法在嗜酸性胃肠道疾病中是否具有临床实用价值；2.EGID的嗜酸性炎症特征是否是IgE依赖的过程？ 研究的初步分析表明，所有受试者对奥马珠单抗都有很好的耐受性。奥马珠单抗治疗有效地阻断了EG患者的IgE，表现为过敏原驱动的嗜碱性粒细胞活化的100-1000倍的转变和游离IgE的减少。奥马珠单抗治疗使受试者外周血嗜酸性粒细胞显著下降。症状。目前的工作集中在肠道活检的分析上，以检查奥马珠单抗对嗜酸性粒细胞渗透的影响。

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.