Oesophageal eosinophilia accompanies food allergy to hen egg white protein in young pigs

Abstract

Clin Exp Allergy. 2020;50:95-104. wileyonlinelibrary.com/journal/cea | 95 Abstract Background: Esophagitis with eosinophilia, inflammation, and fibrosis represent a chronic condition in humans with food allergies.Objective: In this investigation, we asked whether esophagitis with an eosinophilic component is observed in young pigs rendered allergic to hen egg white protein (HEWP). Methods:Food allergy was induced in young pigs using two protocols. In one protocol, sensitized pigs were challenged by gavage with a single dose of HEWP.Clinical signs were monitored for 24 hours, and then, gastrointestinal (GI) tissues were collected for histological examination. The phenotype of circulating, ovalbumin (OVA)-specific T cells also was examined in HEWP challenged animals. In the second protocol, sensitized animals were fed HEWP for 28 days. Animals were then examined by endoscopy and gastrointestinal tissues collected for histological examination. Results:In pigs challenged by gavage with HEWP, clinical signs were noted in 5/6 pigs including diarrhoea, emesis, and skin rash. Clinical signs were not seen in any control group. Histological analysis revealed significant levels of oesophageal eosinophilic infiltration (P < .05) in 4/6 of these animals, with two also displaying eosinophilic infiltration in the stomach. Eosinophils were not increased in ileum or colon samples.Increased numbers of circulating, OVA-specific CD4 + T cells also were observed in pigs that received HEWP by gavage. In the group of animals fed HEWP, endoscopy revealed clinical signs of esophagitis including oedema, granularity, white spots, and furrowing, while histology revealed oedema, immune cell infiltration, and basal zone hyperplasia. Conclusions and Clinical Relevance:Food allergy in the pig can be associated with esophagitis based on histological and endoscopic findings, including eosinophilic infiltration. The young pig may, therefore, be a useful large animal model for the study of eosinophilic esophagitis in humans. K E Y W O R D Sanimal model, eosinophil, esophagitis, food allergy, swine

In vivo optical endomicroscopy: two decades of translational research towards next generation diagnosis of eosinophilic esophagitis

“…10). In the next phase, an animal feasibility study will be conducted in a swine model expressing esophageal strictures (and potentially esophageal eosinophilia [143]) in vivo. A first-in-human study in healthy subjects and EoE patients will then conclude the second phase of the project.…”

Developments in the field of allergy in 2020 through the eyes of Clinical and Experimental Allergy

“…Some sounded a cautionary note-that reintroduction failure after tolerating a food challenge in adults is common, increases over time and is primarily due to atypical symptoms 84 and that anaphylaxis during food challenge may be refractory to intramuscular adrenaline, suggesting that protocols to guide the careful use of peripherally administered intravenous adrenaline may be advisable in food challenge units, for use in these rare cases of refractory anaphylaxis. 85 Other pre-clinical studies support the development of new biomarkers for improved food allergy diagnosis 86,87 and the development of new ways to prevent and treat food allergy. [88][89][90]…”

Developments allergy in 2019 through the eyes of clinical and experimental allergy, part I mechanisms

“…46 Plundrich and colleagues examined whether food (hen egg white protein) induced allergy in young pigs induced an EoE like phenotype. 47 The advantage of the pig system is that pig oesophagus is anatomically similar to humans, non-keratinized and display oesophageal submucosal glands and is similar in size to the human oesophagus allowing for the use of endoscopy. 48 The authors showed that challenge of hen Collectively, these studies suggest that the pig may be an effective model to study immunological processes that drive some EoEassociated oesophageal epithelia remodelling features and to study the role of the underlying oesophageal inflammatory component in EoE with endoscopic features.…”

“…However, the oesophagus of the mouse is anatomically different to human (keratinized versus non‐keratinized) which greatly limits interpretation and translatability of studies derived from using this animal model system 46 . Plundrich and colleagues examined whether food (hen egg white protein) induced allergy in young pigs induced an EoE like phenotype 47 . The advantage of the pig system is that pig oesophagus is anatomically similar to humans, non‐keratinized and display oesophageal submucosal glands and is similar in size to the human oesophagus allowing for the use of endoscopy 48 .…”