Background: Food allergy may affect the gastrointestinal tract and eosinophilia is often associated with allergic gastrointestinal disorders. Allergy to peanuts is a life-threatening condition and ...effective and safe treatments still need to be developed. The present study aimed to evaluate the effects of sustained oral exposure to peanuts on the esophageal and jejunal mucosa in sensitized mice. We also evaluated the effects of desensitization with epicutaneous immunotherapy (EPIT) on these processes. Methods: Mice were sensitized by gavages with whole peanut protein extract (PPE) given with cholera toxin. Sensitized mice were subsequently exposed to peanuts via a specific regimen and were then analysed for eosinophilia in the esophagus and gut. We also assessed mRNA expression in the esophagus, antibody levels, and peripheral T-cell response. The effects of EPIT were tested when intercalated with sensitization and sustained oral peanut exposure. Results: Sustained oral exposure to peanuts in sensitized mice led to severe esophageal eosinophilia and intestinal villus sub-atrophia, i.e. significantly increased influx of eosinophils into the esophageal mucosa (136 eosinophils/mm2) and reduced villus/crypt ratios (1.660.15). In the sera, specific IgE levels significantly increased as did secretion of Th2 cytokines by peanut-reactivated splenocytes. EPIT of sensitized mice significantly reduced Th2 immunological response (IgE response and splenocyte secretion of Th2 cytokines) as well as esophageal eosinophilia (50 eosinophils/mm2, p,0.05), mRNA expression of Th2 cytokines in tissue - eotaxin (p,0.05), IL-5 (p,0.05), and IL-13 (p,0.05) -, GATA-3 (p,0.05), and intestinal villus sub-atrophia (2.360.15). EPIT also increased specific IgG2a (p,0.05) and mRNA expression of Foxp3 (p,0.05) in the esophageal mucosa. Conclusions: Gastro-intestinal lesions induced by sustained oral exposure in sensitized mice are efficaciously treated by allergen specific EPIT.
Background: Food allergy may affect the gastrointestinal tract and eosinophilia is often associated with allergic gastrointestinal disorders. Allergy to peanuts is a life-threatening condition and ...effective and safe treatments still need to be developed. The present study aimed to evaluate the effects of sustained oral exposure to peanuts on the esophageal and jejunal mucosa in sensitized mice. We also evaluated the effects of desensitization with epicutaneous immunotherapy (EPIT) on these processes. Methods: Mice were sensitized by gavages with whole peanut protein extract (PPE) given with cholera toxin. Sensitized mice were subsequently exposed to peanuts via a specific regimen and were then analysed for eosinophilia in the esophagus and gut. We also assessed mRNA expression in the esophagus, antibody levels, and peripheral T-cell response. The effects of EPIT were tested when intercalated with sensitization and sustained oral peanut exposure. Results: Sustained oral exposure to peanuts in sensitized mice led to severe esophageal eosinophilia and intestinal villus sub-atrophia, i.e. significantly increased influx of eosinophils into the esophageal mucosa (136 eosinophils/mm2) and reduced villus/crypt ratios (1.660.15). In the sera, specific IgE levels significantly increased as did secretion of Th2 cytokines by peanut-reactivated splenocytes. EPIT of sensitized mice significantly reduced Th2 immunological response (IgE response and splenocyte secretion of Th2 cytokines) as well as esophageal eosinophilia (50 eosinophils/mm2, p,0.05), mRNA expression of Th2 cytokines in tissue - eotaxin (p,0.05), IL-5 (p,0.05), and IL-13 (p,0.05) -, GATA-3 (p,0.05), and intestinal villus sub-atrophia (2.360.15). EPIT also increased specific IgG2a (p,0.05) and mRNA expression of Foxp3 (p,0.05) in the esophageal mucosa. Conclusions: Gastro-intestinal lesions induced by sustained oral exposure in sensitized mice are efficaciously treated by allergen specific EPIT.
BackgroundEosinophilia is often linked to allergic gastrointestinaldisorders linked to food allergy. EPIT using Viaskin®device has been described as a therapeutic method infood allergy. We developed ...a model of mice sensitizedto peanut, exhibiting EoE and AE after exclusive feedingwith peanut protein extracts (PPE). This study was conductedin order to evaluate the efficacy of EPIT.MethodsAfter oral sensitization with PPE and cholera toxin, 30BALB/c mice were treated weekly during 8 weeks byPPE skin applications (EPIT), 20 mice were not treated(Sham) and 10 mice constituted the control group (C).Mice were then exclusively fed with PPE. Specific IgE,IgG1 and IgG2a were monitored during immunotherapy.Esophageal and jejunal samples were taken for histologicalanalyses.ResultssIgE increased after oral sensitization, respectively 0.207±0.03 and 0.214±0.04 μg/ml, in EPIT and Sham, withundetectable values in C. Following EPIT, sIgEdecreased and sIgG2a increased, respectively 0.139±0.01vs 0.166±0.01 μg/ml (EPIT vs Sham, p<0.05) and 14.96±0.60 vs 4.73±1.75 μg/ml (p<0.05). Esophageal eosinophilicinfiltration (measured in 6 high power fields) washigher in Sham, 136±32, than in EPIT, 50±12 (p<0.05)and C, 7±3 cells/mm2 (p<0.01). Esophagus mucosathickness was increased in Sham compared to EPIT andC (p<0.001). Sham group exhibited higher mRNA levelsof cytokines than EPIT: eotaxin (p<0.05), IL-5 (p<0.05),IL-13 (p<0.05). The mRNA levels of these cytokines inEPIT were similar to C. The expression of Foxp3mRNA increased significantky after EPIT comparedwith Sham and C (p<0.05). The jejunal villus/crypt ratiowas lower in Sham than in EPIT and C, respectively 1.6±0.1 vs 2.3±0.2 (p<0.01) and 2.4±0.1 (p<0.001). Eosinophilicinfiltration in jejunum was increased in Shamcompared to EPIT (p<0.01) and C (p<0.001).ConclusionEPIT is effective in preventing EoE and AE induced byoral challenge in mice sensitized to peanut.
Background: Food allergy may affect the gastrointestinal tract and eosinophilia is often associated with allergic gastrointestinal disorders. Allergy to peanuts is a life-threatening condition and ...effective and safe treatments still need to be developed. The present study aimed to evaluate the effects of sustained oral exposure to peanuts on the esophageal and jejunal mucosa in sensitized mice. We also evaluated the effects of desensitization with epicutaneous immunotherapy (EPIT) on these processes. Methods: Mice were sensitized by gavages with whole peanut protein extract (PPE) given with cholera toxin. Sensitized mice were subsequently exposed to peanuts via a specific regimen and were then analysed for eosinophilia in the esophagus and gut. We also assessed mRNA expression in the esophagus, antibody levels, and peripheral T-cell response. The effects of EPIT were tested when intercalated with sensitization and sustained oral peanut exposure. Results: Sustained oral exposure to peanuts in sensitized mice led to severe esophageal eosinophilia and intestinal villus sub-atrophia, i.e. significantly increased influx of eosinophils into the esophageal mucosa (136 eosinophils/mm2) and reduced villus/crypt ratios (1.660.15). In the sera, specific IgE levels significantly increased as did secretion of Th2 cytokines by peanut-reactivated splenocytes. EPIT of sensitized mice significantly reduced Th2 immunological response (IgE response and splenocyte secretion of Th2 cytokines) as well as esophageal eosinophilia (50 eosinophils/mm2, p,0.05), mRNA expression of Th2 cytokines in tissue - eotaxin (p,0.05), IL-5 (p,0.05), and IL-13 (p,0.05) -, GATA-3 (p,0.05), and intestinal villus sub-atrophia (2.360.15). EPIT also increased specific IgG2a (p,0.05) and mRNA expression of Foxp3 (p,0.05) in the esophageal mucosa. Conclusions: Gastro-intestinal lesions induced by sustained oral exposure in sensitized mice are efficaciously treated by allergen specific EPIT.
Ankum Hans, Platelle Henri, Cauchies Jean-Marie, Stas Françoise, Roelofsen C.-G., Moorman van Kappen O., Hansotte Georges, Demars-Sion Véronique, D'Arras d'Haudrecy L., Dupont-Bouchat S. Société ...d'histoire du Droit et des Institutions des Pays Flamands, Picards et Wallons Journées Internationales de Namur (20-23 mai 1982). In: Revue du Nord, tome 65, n°256, Janvier-mars 1983. Archéologie. pp. 221-231.
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