Treatment of gastric eosinophilia by epicutaneous immunotherapy in piglets sensitized to peanuts

Background: Eosinophilic gastrointestinal disorders (EGIDs) are hypersensitivity disorders frequently triggered by food allergy and manifested by mucosal eosinophilic infiltration at any level of the gastrointestinal tract. This study established a model of gastric eosinophilia in peanut-sensitized piglets to evaluate the efficacy of epicutaneous immunotherapy (EPIT) for its treatment. Methods: Experiments were carried out in piglets first sensitized by three intraperitoneal injections of peanut protein extract (PPE) with adjuvant, and then given PPE orally for 10 days, a sequence leading to gastric eosinophilia assessed by endoscopy. For 3 months, eight piglets received active EPIT, using Viaskin +/- loaded with PPE, applied daily on the ear, while eight received placebo EPIT (Placebo). Piglets were exposed to a second 10-day period of PPE orally. Lesions were scored by endoscopy on the last day of PPE exposure. After killing, all parts of the digestive tract were analysed by a pathologist unaware of the piglets' status. IgE response was measured, and mechanistic parameters were analysed in the spleen. Results: After sensitization, a significant increase of total IgE was observed in sensitized compared to naive animals (61.1 +/- 13.3 vs 27.8 +/- 6 ng/mL, P < .01). Following oral intake of PPE, sensitized piglets developed moderate gastritis compared to naive piglets (1.5 vs 1.0, median score). After 3 months of immunotherapy, median IgE was significantly reduced in EPIT vs placebo piglets (61.4 +/- 16.3 vs 105.9 +/- 25.6 ng/mL, P <.01). Active EPIT significantly reduced gastric mucosal lesions induced by PPE oral intake (macroscopic score 0 [0-2] vs 2 [1-3], P <.01, respectively, active vs placebo) and gastric mucosa eosinophils counts (239 eosinophils/mm(2) [59-645] vs 2554 eosinophils/mm(2) [462-8057], P<.01, respectively active vs placebo). GATA-3, IL-5 and eotaxin mRNA expression decreased significantly after EPIT (P<.05). Conclusions: This study describes a large animal model of gastric eosinophil in peanut- sensitized piglets. Utilizing this model, we demonstrated the efficacy of EPIT in treating peanut-induced EGIDs.