THE NATURAL HISTORY OF FOOD - PROTEIN INDUCED ENTEROCOLITIS SYNDROME

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 食物蛋白诱导的肠结肠炎综合征(FPIES)是一种严重的婴儿细胞介导的非IgE抗体相关的食物超敏反应，典型的由牛奶和/或大豆(1-6)引起，其特征是大量呕吐和腹泻，20%的患者进展为脱水和休克。最初的报告描述了在摄入牛奶或大豆配方奶粉后出现这些症状的年轻婴儿。患者通过不含牛奶和大豆的饮食迅速康复，但在饮食停用一段时间后，摄入这些蛋白会在摄入后2-3小时内触发亚急性症状，并伴随外周血多形核白细胞计数的升高。 尽管有大米和其他食物引起FPIES的病例报告，但固体食物蛋白并未被很好地识别为潜在的引发FPIES的因素。然而，在我们的临床实践中，我们观察到婴儿由牛奶和/或大豆以外的饮食蛋白引起的FPIES，包括几种以前从未报告过会导致这种疾病的食物(燕麦、大麦、南瓜、红薯)。我们建议研究FPIES，以更好地描述这种综合征的自然病史，描述对食物过敏原的免疫反应的病理生理学，并确定耐受性的标志。 FPIES是一种严重的呕吐和腹泻综合征，通常由9个月以下婴儿的牛奶或大豆蛋白引起。大约一半受影响的婴儿对牛奶和大豆蛋白都有反应。一些患者出现大量呕吐的剧烈症状，有或没有腹泻，可能进展为酸血症和休克。相关的高铁血红蛋白血症被认为是由于肠道中硝酸盐的增加引起的血红素氧化增加所致。活检显示隐窝脓肿，结肠内弥漫性炎细胞和浆细胞浸润，小肠水肿伴轻度绒毛损伤。诊断通常基于临床标准，如有必要，可通过标准化的口服询问方案进行诊断。这种疾病是由细胞介导的，通常在没有阳性过敏点刺试验或血清过敏原特异性IgE抗体的情况下发生。最近的研究表明，乳汁刺激时，乳汁分泌的肿瘤坏死因子-α主要由T细胞介导。转化生长因子-β(转化生长因子-β)相对缺乏表达也可能参与其中。在两年内，60%的牛奶和20%的大豆诱导的FPIES痊愈。固体食物蛋白不是公认的潜在罪魁祸首，但文献报道和我们的临床经验表明，谷物、肉类、水果和蔬菜能够诱发FPIES。尽管FPIES的患病率尚不清楚，但考虑到其他食物过敏综合征的患病率不断增加，FPIES的上升是可以预期的。因此，了解这种疾病的自然病史对于更有效地治疗患者是很重要的。我们建议对儿童进行前瞻性研究，以确定获得耐受性的平均年龄以及与耐受性发展有关的机制。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Food Protein-Induced Enterocolitis Syndrome (FPIES) is a severe infantile cell-mediated, non-IgE antibody-associated food hypersensitivity caused typically by cow's milk and/or soy (1-6) FPIES is characterized by profuse vomiting and diarrhea, with progression to dehydration and shock in 20% of patients. Inital reports described young infants with these symptoms following ingestion of cow's milk or soy-based formula. Patients rapidly recover with milk- and soy-free diets, but ingestion of these proteins following a period of dietary elimination triggers subacute symptoms over 2-3 hours following ingestion with an associated elevation of the peripheral blood polymorphonuclear leukocyte count. Although there are case reports of rice and other foods causing FPIES, solid food proteins are not well recognized as potential triggers of FPIES. However, in our clinical practice we have observed infants with FPIES due to dietary food proteins other than cow's milk and/or soy, including several foods (oat, barley, squash, sweet potato) never before reported to cause this disorder. We propose to investigate FPIES to better characterize the natural history of this syndrome, characterize pathophysiology of the immune responses to food allergens, and to determine the markers of tolerance. FPIES is a severe syndrome of vomiting and diarrhea typically caused by cow's milk or soy protein in infants younger than 9 months. Approximately half of affected infants react to both milk and soy proteins. Some patients present with dramatic symptoms of profuse vomiting, with or without diarrhea, which may progress to acidemia and shock. Associated methemoglobinemia is thought to result from increased heme oxidation caused by an elevation of nitrates in the intestine. Biopsies show crypt abscesses, diffuse inflammatory cell infiltrates with plasma cells in the colon, and edema with mild villous injury in the small intestine. The diagnosis is typically made on the basis of clinical criteria and, if necessary, by a standardized oral challenge protocol. The disorder is cell-mediated and occurs typically without positive allergy prick skin tests or serum allergen-specific IgE antibodies. Recent studies suggest that FPIES is predominantly mediated by T cells, which have been shown to secrete TNF-alpha upon milk stimulation. A relative lack of expression of transforming growth factor - beta (TGF-beta) may also be involved. Within 2 years, 60% of milk and 20% of soy-induced FPIES resolves. Solid food proteins are not recognized potential culprits but reports from the literature as well as our clinical experience indicate that grains, meats, fruits and vegetables are capable of inducing FPIES. Although the prevalence of FPIES is unknown, considering increasing prevalence of other food hypersensitivity syndromes, a rise in FPIES may be expected. Therefore it is important to characterize the natural history of this disorder for more efficient managements of the patients. We propose to prospectively study FPIES in children to determine the average age of achieving tolerance as well as mechanisms involved in tolerance development.