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Treatment of gastric eosinophilia by epicutaneous immunotherapy in piglets sensitized to peanuts
Author(s) -
Mondoulet L.,
Kalach N.,
Dhelft V.,
Larcher T.,
DelayreOrthez C.,
Benhamou P. H.,
Spergel J.,
Sampson H. A.,
Dupont C.
Publication year - 2017
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/cea.13037
Subject(s) - medicine , eosinophilia , immunoglobulin e , gastroenterology , placebo , allergy , sensitization , eosinophil , immunology , stomach , gastrointestinal tract , immunotherapy , gastritis , antibody , pathology , immune system , asthma , alternative medicine
Summary Background Eosinophilic gastrointestinal disorders ( EGID s) 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/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 EGID s.