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

Clin Exp Allergy. 2017 Dec;47(12):1640-1647. doi: 10.1111/cea.13037. Epub 2017 Oct 20.

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 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 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, 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/mm2 [59-645] vs 2554 eosinophils/mm2 [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.

Keywords: EGIDs; animal models; eosinophils; epicutaneous; food allergy; gastritis; immunotherapy.

MeSH terms

  • Allergens / immunology*
  • Animals
  • Arachis / immunology*
  • Biomarkers
  • Desensitization, Immunologic* / methods
  • Disease Models, Animal
  • Endoscopy, Gastrointestinal
  • Enteritis / diagnosis
  • Enteritis / immunology*
  • Enteritis / therapy
  • Eosinophilia / diagnosis
  • Eosinophilia / immunology*
  • Eosinophilia / therapy
  • Female
  • Gastritis / diagnosis
  • Gastritis / immunology*
  • Gastritis / therapy
  • Immunization
  • Immunoglobulin E / immunology
  • Male
  • Peanut Hypersensitivity / diagnosis
  • Peanut Hypersensitivity / immunology*
  • Peanut Hypersensitivity / therapy
  • Treatment Outcome

Substances

  • Allergens
  • Biomarkers
  • Immunoglobulin E

Supplementary concepts

  • Eosinophilic enteropathy