THE NATURAL HISTORY OF FOOD - PROTEIN INDUCED ENTEROCOLITIS SYNDROME

食物的自然史 - 蛋白质诱发的小肠结肠炎综合征

• 批准号: 7718120
• 负责人: Anna Halina Nowak-Wegrzyn
• 金额: $ 2.34万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7718120
• 关键词: Abscess; Affect; Age; Allergens; Antibodies; Barley; Biopsy; Case Study; Cattle; Cells; Cereals; Child; Clinical; Colon; Computer Retrieval of Information on Scientific Projects Database; Dehydration; Development; Diagnosis; Diarrhea; Diet; Diffuse; Disease; Edema; Elevation; Enterocolitis; Food; Food Hypersensitivity; Functional disorder; Funding; Genus Cola; Grant; Heme; Hour; Hypersensitivity; Hypersensitivity skin testing; IgE; Immune response; Infant; Inflammatory; Ingestion; Injury; Institution; Intestines; Literature; Meat; Mediating; Methemoglobinemia; Milk; Natural History; Nitrates; Oats; Oral; Patients; Plasma Cells; Prevalence; Proteins; Protocols documentation; Relative (related person); Reporting; Research; Research Personnel; Resources; Rice; Serum; Shock; Small Intestines; Solid; Source; Soy Milk; Soy Proteins; Squash; Sweet potato - dietary; Symptoms; Syndrome; T-Lymphocyte; Thinking; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha; United States National Institutes of Health; Villous; Vomiting; White Blood Cell Count procedure; base; experience; food allergen; fruits and vegetables; human TNF protein; infancy; neutrophil; nitrate; oxidation; peripheral blood; soy

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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 食物蛋白诱导的小肠结肠炎综合征（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，通常由牛奶和/或大豆引起（1-6）FPIES的特征是大量呕吐和腹泻，20%的患者进展为脱水和休克。 最初的报告描述了摄入牛奶或大豆配方奶粉后出现这些症状的幼儿。 患者通过无牛奶和大豆饮食迅速恢复，但在饮食消除期后摄入这些蛋白质会在摄入后2-3小时内引发亚急性症状，并伴有外周血多形核白细胞计数升高。 虽然有稻米和其他食物引起FPIES的病例报告，但固体食物蛋白质并没有被很好地认识到是FPIES的潜在触发因素。 然而，在我们的临床实践中，我们观察到婴儿因牛奶和/或大豆以外的膳食蛋白质而患有FPIES，包括以前从未报道过导致这种疾病的几种食物（燕麦，大麦，南瓜，甘薯）。 我们建议调查FPIES，以更好地表征这种综合征的自然史，表征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物。 FPIES是一种严重的呕吐和腹泻综合征，通常由9个月以下的婴儿的牛奶或大豆蛋白引起。 大约一半的受影响婴儿对牛奶和大豆蛋白都有反应。 一些患者出现剧烈呕吐的症状，伴或不伴腹泻，可能会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肠内硝酸盐升高引起的血红素氧化增加引起的。 活组织检查显示结肠腺囊肿，弥漫性炎性细胞浸润伴浆细胞浸润，小肠水肿伴轻度绒毛损伤。 诊断通常基于临床标准进行，如果需要，通过标准化的口服激发方案进行。 这种疾病是细胞介导的，通常在没有阳性过敏点刺皮肤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，FPIES主要由T细胞介导，T细胞已被证明在乳汁刺激后分泌TNF-α。 转化生长因子-β（TGF-β）表达的相对缺乏也可能涉及。 在两年内，60%的牛奶和20%的大豆引起的FPIES解决。 固体食物蛋白质不是公认的潜在罪魁祸首，但文献报告以及我们的临床经验表明，谷物，肉类，水果和蔬菜能够诱导FPIES。 虽然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，预计FPIES的患病率可能会上升。 因此，重要的是要描述这种疾病的自然史，以便更有效地管理患者。 我们建议在儿童中前瞻性研究FPIES，以确定实现耐受性的平均年龄以及耐受性发展所涉及的机制。