Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA, USA.
Department of Medicine, Harvard Medical School, Boston, MA, USA.
Allergy. 2017 Dec;72(12):1916-1924. doi: 10.1111/all.13219. Epub 2017 Jul 14.
Food allergies are a growing health problem, and the development of therapies that prevent disease onset is limited by the lack of adjuvant-free experimental animal models. We compared allergic sensitization in patients with food allergy or Wiskott-Aldrich syndrome (WAS) and defined whether spontaneous disease in Was mice recapitulates the pathology of a conventional disease model and/or human food allergy.
Comparative ImmunoCAP ISAC microarray was performed in patients with food allergy or WAS. Spontaneous food allergy in Was mice was compared to an adjuvant-based model in wild-type mice (WT-OVA/alum). Intestinal and systemic anaphylaxis was assessed, and the role of the high-affinity IgE Fc receptor (FcεRI) in allergic sensitization was evaluated using Was Fcer1a mice.
Polysensitization to food was detected in both WAS and food-allergic patients which was recapitulated in the Was model. Oral administration of ovalbumin (OVA) in Was mice induced low titers of OVA-specific IgE compared to the WT-OVA/alum model. Irrespectively, 79% of Was mice developed allergic diarrhea following oral OVA challenge. Systemic anaphylaxis occurred in Was mice (95%) with a mortality rate >50%. Spontaneous sensitization and intestinal allergy occurred independent of FcεRI expression on mast cells (MCs) and basophils.
Was mice provide a model of food allergy with the advantage of mimicking polysensitization and low food-antigen IgE titers as observed in humans with clinical food allergy. This model will facilitate studies on aberrant immune responses during spontaneous disease development. Our results imply that therapeutic targeting of the IgE/FcεRI activation cascade will not affect sensitization to food.
食物过敏是一个日益严重的健康问题，由于缺乏无佐剂的实验动物模型，预防疾病发生的治疗方法的发展受到限制。我们比较了食物过敏或威特综合征（WAS）患者的过敏致敏情况，并确定了自发性疾病在 Was 小鼠中是否再现了传统疾病模型和/或人类食物过敏的病理学。
对食物过敏或 WAS 患者进行比较免疫 CAP ISAC 微阵列分析。比较了 Was 小鼠的自发性食物过敏与野生型小鼠（WT-OVA/明矾）的基于佐剂的模型。评估了肠道和全身过敏反应，并使用具有高亲和力 IgE Fc 受体（FcεRI）的 Was Fcer1a 小鼠评估了其在过敏致敏中的作用。
在 WAS 和食物过敏患者中均检测到对食物的多敏化，这在 Was 模型中得到了再现。在 Was 小鼠中口服卵清蛋白（OVA）诱导的 OVA 特异性 IgE 滴度低于 WT-OVA/明矾模型。然而，79%的 Was 小鼠在口服 OVA 挑战后发展为过敏性腹泻。在 Was 小鼠中发生全身过敏反应（95%），死亡率>50%。自发性致敏和肠道过敏发生与肥大细胞（MCs）和嗜碱性粒细胞上的 FcεRI 表达无关。
Was 小鼠提供了一种食物过敏模型，其优点是模拟多敏化和低食物抗原 IgE 滴度，如临床食物过敏患者所见。该模型将有助于研究自发性疾病发展过程中的异常免疫反应。我们的结果表明，针对 IgE/FcεRI 激活级联的治疗靶向不会影响对食物的致敏。
