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: 7380540
• 负责人: Anna Halina Nowak-Wegrzyn
• 金额: $ 1.07万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-17 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7380540
• 关键词: cow; diarrhea; food; milk; proteins; syndrome

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.

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中出现。列出的机构是中心的机构，不一定是研究者的机构。食物蛋白诱发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 的特点是严重呕吐和腹泻，且病情进展20%的患者出现脱水和休克。最初的报告描述了小婴儿在摄入牛奶或豆基配方奶粉后出现这些症状。患者通过不含牛奶和大豆的饮食可以迅速康复，但在一段时间的饮食消除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，并导致外周血多形核白细胞计数升高。 尽管有大米和其他食物引起 FPIES 的病例报告，但固体食物蛋白质尚未被充分认识为 FPIES 的潜在诱因。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，包括几种以前从未报道过会导致这种疾病的食物（燕麦、大麦、南瓜、甘薯）。我们建议研究 FPIES，以更好地表征该综合征的自然史，表征对食物过敏原的免疫反应的病理生理学，并确定耐受标记。 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。一些患者出现严重呕吐症状，伴有或不伴有腹泻，可能会发展为酸血症和休克。相关的高铁血红蛋白血症被认为是由于肠道内硝酸盐升高导致血红素氧化增加所致。活检显示隐窝脓肿，结肠内弥漫性炎症细胞与浆细胞浸润，小肠水肿伴轻度绒毛损伤。诊断通常是根据临床标准做出的，如有必要，还可以通过标准化的口服挑战方案进行诊断。该疾病是细胞介导的，通常在过敏点刺皮肤试验或血清过敏原特异性 IgE 抗体不呈阳性的情况下发生。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会分泌 TNF-α。转化生长因子-β（TGF-β）的表达相对缺乏也可能与此有关。 2 年内，60% 的牛奶和 20% 的大豆引起的 FPIES 消失。固体食物蛋白未被认为是潜在的罪魁祸首，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。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，预计 FPIES 的增加是可以预期的。因此，为了更有效地管理患者，描述这种疾病的自然史非常重要。我们建议对儿童进行前瞻性研究 FPIES，以确定达到耐受性的平均年龄以及耐受性发展的机制。