Division of Pediatric Allergy and Immunology, Mount Sinai School of Medicine, New York, NY 10029, USA.
J Allergy Clin Immunol. 2012 Jun;129(6):1579-1587.e1. doi: 10.1016/j.jaci.2012.04.009. Epub 2012 May 1.
Oral immunotherapy (OIT) is a promising treatment for food allergy. Studies are needed to elucidate mechanisms of clinical protection and to identify safer and potentially more efficacious methods for desensitizing patients to food allergens.
We established a mouse model of OIT to determine how the dose or form of antigen may affect desensitization and to identify mechanisms of desensitization.
Increasing doses of egg white or ovomucoid as OIT were administered orally to sensitized mice. The impact of OIT on anaphylaxis elicited by oral allergen challenge was determined. Allergen-specific antibody and cytokine responses and mast cell and basophil activation in response to OIT were measured. Gene expression in the small intestine was studied by microarray and real-time PCR.
OIT resulted in desensitization but not tolerance of mice to the allergen. OIT did not result in desensitization of systemic effector cells, and protection was localized to the gastrointestinal tract. OIT was associated with significant changes in gene expression in the jejunum, including genes expressed by intestinal epithelial cells. Extensively heated ovomucoid that does not trigger anaphylaxis when given orally to sensitized mice was as efficacious as native ovomucoid in desensitizing mice.
OIT results in clinical protection against food-induced anaphylaxis through a novel mechanism that is localized to the intestinal mucosa and is associated with significant changes in small intestinal gene expression. Extensively heating egg allergen decreases allergenicity and increases safety while still retaining the ability to induce effective desensitization.
口服免疫疗法（OIT）是治疗食物过敏的一种很有前途的方法。需要进行研究以阐明临床保护的机制，并确定更安全、更有效的使患者对食物过敏原脱敏的方法。
我们建立了 OIT 的小鼠模型，以确定抗原的剂量或形式如何影响脱敏，并确定脱敏的机制。
将递增剂量的蛋清或卵类黏蛋白作为 OIT 经口给予致敏小鼠。通过口服过敏原挑战确定 OIT 对过敏反应的影响。测量 OIT 对过敏原特异性抗体和细胞因子反应以及肥大细胞和嗜碱性粒细胞活化的影响。通过微阵列和实时 PCR 研究小肠中的基因表达。
OIT 导致了小鼠对过敏原的脱敏，但不是耐受。OIT 没有导致全身效应细胞的脱敏，保护作用局限于胃肠道。OIT 与空肠中基因表达的显著变化相关，包括肠上皮细胞表达的基因。经口给予致敏小鼠后不会引发过敏反应的高度加热卵类黏蛋白与天然卵类黏蛋白一样有效，可使小鼠脱敏。
OIT 通过一种新型机制导致临床保护，防止食物引起的过敏反应，该机制局限于肠道黏膜，并与小肠基因表达的显著变化相关。充分加热过敏原可以降低过敏原性，提高安全性，同时仍然保留有效脱敏的能力。
