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

Abstract

Background

Eosinophilic Gastrointestinal Disorders (EGIDs) are hypersensitivity disorders frequently triggered by food allergy and manifested by mucosal eosinophilic infiltration at any level of the gastro-intestinal 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 3 intra-peritoneal 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, 8 piglets received active EPIT, using Viaskin^® loaded with PPE, applied daily on the ear, while 8 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 sacrifice, all parts of the digestive tract were analysed by a pathologist unaware of the piglets' status. IgE response was measured and mechanistic parameters were analyzed 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<0.01). 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<0.01). Active EPIT significantly reduced gastric mucosal lesions induced by PPE oral intake (macroscopic score 0 [0-2] vs 2 [1-3], p<0.01, respectively active vs placebo) and gastric mucosa eosinophils counts (239 eosinophils/mm² [59-645] vs 2554 eosinophils/mm² [462-8057], p<0.01, respectively active vs placebo). GATA-3, IL-5 and eotaxin mRNA expression decreased significantly after EPIT (p<0.05).

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.

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