Oral immunotherapy induces local protective mechanisms in the gastrointestinal mucosa.
Oral immunotherapy induces local protective mechanisms in the gastrointestinal mucosa.
复制标题
DOI：
10.1016/j.jaci.2012.04.009
复制
发表时间：
2012-06
影响因子：
14.2
通讯作者：
Berin, M. Cecilia
中科院分区：
文献类型：
--
作者：
Leonard, Stephanie A.;Martos, Gustavo;Wang, Wei;Nowak-Wegrzyn, Anna;Berin, M. Cecilia
口服免疫疗法（OIT）是一种很有前途的食物过敏治疗方法。需要进行研究以阐明临床保护机制，并确定更安全和潜在更有效的方法来使患者对食物过敏原脱敏。我们建立了OIT小鼠模型，以确定抗原的剂量或形式如何影响脱敏，并确定脱敏机制。将递增剂量的鸡蛋白色或卵类粘蛋白作为OIT经口给予致敏小鼠。测定OIT对口服过敏原激发引起的过敏反应的影响。测定了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对OIT的活化反应。通过微阵列和实时荧光PCR研究小肠中的基因表达。OIT导致小鼠对过敏原的脱敏，但不耐受。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。广泛加热卵类粘蛋白，不触发过敏反应时，口服给药致敏小鼠是有效的天然卵类粘蛋白在脱敏小鼠。OIT通过一种定位于肠粘膜并与小肠基因表达的显著变化相关的新机制，对食物诱导的过敏反应产生临床保护作用。广泛加热鸡蛋过敏原可降低过敏原性并增加安全性，同时仍保留诱导有效脱敏的能力。
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 in order to determine how 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. 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 was 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.
登录
查看更多内容
影响因子：
15.9
作者：
Kraus, TA;Brimnes, J;Mayer, L
通讯作者：
Mayer, L
影响因子：
2.6
作者：
Castells, Mariana
通讯作者：
Castells, Mariana
影响因子：
4.4
作者：
Boyce, Joshua A.;Assa'a, Amal;Schwaninger, Julie M.
通讯作者：
Schwaninger, Julie M.
影响因子：
14.2
作者：
Sicherer, Scott H.
通讯作者：
Sicherer, Scott H.
DOI：
10.1016/j.jaci.2011.01.057
发表时间：
2011-04
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Martos G;Lopez-Exposito I;Bencharitiwong R;Berin MC;Nowak-Węgrzyn A
通讯作者：
Nowak-Węgrzyn A