Teuber Suzanne S, Del Val Gregorio, Morigasaki Susumu, Jung Hye Rim, Eisele Pamela H, Frick Oscar L, Buchanan Bob B
Department of Internal Medicine, University of California, Davis, School of Medicine, Davis, CA 95616, USA.
J Allergy Clin Immunol. 2002 Dec;110(6):921-7. doi: 10.1067/mai.2002.130056.
Animal models are needed that mimic human IgE-mediated peanut and tree nut allergy. Atopic dogs have been previously used in a model of food allergy to cow's milk, beef, wheat, and soy, with the demonstration of specific IgE production and positive oral challenges similar to those seen in human subjects.
We sought to sensitize dogs to peanut, walnut, and Brazil nut and to assess whether sensitization is accompanied by clinical reactions and whether there is cross-reactivity among the different preparations.
Eleven dogs were sensitized subcutaneously by using an established protocol with 1 microg each of peanut, English walnut, or Brazil nut protein extracts in alum first at birth and then after modified live virus vaccinations at 3, 7, and 11 weeks of age. The dogs were sensitized to other allergens, including soy and either wheat or barley. Intradermal skin tests, IgE immunoblotting to nut proteins, and oral challenges were performed with ground nut preparations.
At 6 months of age, the dogs' intradermal skin test responses were positive to the nut extracts. IgE immunoblotting to peanut, walnut, and Brazil nut showed strong recognition of proteins in the aqueous preparations. Each of the 4 peanut- and the 3 Brazil nut-sensitized dogs and 3 of the 4 walnut-sensitized dogs reacted on oral challenge with the corresponding primary immunogen at age 2 years. None of the peanut-sensitized dogs reacted clinically with walnut or Brazil nut challenges. One of the walnut-sensitized dogs had delayed (overnight) vomiting to Brazil nut.
On the basis of measurements of the mean amount of allergen eliciting a skin test response in dogs, the hierarchy of reactivity by skin testing is similar to the clinical experience in human subjects (peanut > tree nuts > wheat > soy > barley). Cross-reactivity, which was not apparent between soy and peanut or tree nuts or between peanut and tree nuts, was slight between walnut and Brazil nut. The results give further support to the dog as a model of human food allergy.
需要能够模拟人类IgE介导的花生和坚果过敏的动物模型。特应性犬此前已被用于牛奶、牛肉、小麦和大豆食物过敏模型，表现出特异性IgE产生以及与人类受试者相似的阳性口服激发试验结果。
我们试图使犬对花生、核桃和巴西坚果致敏，并评估致敏是否伴有临床反应以及不同制剂之间是否存在交叉反应。
11只犬按照既定方案在出生时皮下注射1微克花生、英国核桃或巴西坚果蛋白提取物与明矾的混合物，然后在3、7和11周龄进行改良活病毒疫苗接种后再次注射。这些犬还对其他过敏原致敏，包括大豆以及小麦或大麦。用磨碎的坚果制剂进行皮内皮肤试验、针对坚果蛋白的IgE免疫印迹分析以及口服激发试验。
6月龄时，犬对坚果提取物的皮内皮肤试验反应呈阳性。针对花生、核桃和巴西坚果的IgE免疫印迹分析显示对水性制剂中的蛋白质有强烈识别。4只花生致敏犬、3只巴西坚果致敏犬中的每只以及4只核桃致敏犬中的3只在2岁时对相应的主要免疫原进行口服激发试验时有反应。花生致敏犬中没有一只对核桃或巴西坚果激发试验产生临床反应。一只核桃致敏犬对巴西坚果有延迟（过夜）呕吐反应。
根据在犬中引发皮肤试验反应的变应原平均量的测量结果，皮肤试验的反应性等级与人类受试者的临床经验相似（花生＞坚果＞小麦＞大豆＞大麦）。大豆与花生或坚果之间、花生与坚果之间未表现出明显的交叉反应，核桃与巴西坚果之间的交叉反应轻微。这些结果进一步支持犬作为人类食物过敏模型。
