Document Detail


Oral immunotherapy induces local protective mechanisms in the gastrointestinal mucosa.
MedLine Citation:
PMID:  22554705     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Oral immunotherapy (OIT) is a promising treatment for food allergy. Studies are needed to elucidate mechanisms of clinical protection and to identify safer and potentially more efficacious methods for desensitizing patients to food allergens.
OBJECTIVE: We established a mouse model of OIT to determine how the dose or form of antigen may affect desensitization and to identify mechanisms of desensitization.
METHODS: Increasing doses of egg white or ovomucoid as OIT were administered orally to sensitized mice. The impact of OIT on anaphylaxis elicited by oral allergen challenge was determined. Allergen-specific antibody and cytokine responses and mast cell and basophil activation in response to OIT were measured. Gene expression in the small intestine was studied by microarray and real-time PCR.
RESULTS: OIT resulted in desensitization but not tolerance of mice to the allergen. OIT did not result in desensitization of systemic effector cells, and protection was localized to the gastrointestinal tract. OIT was associated with significant changes in gene expression in the jejunum, including genes expressed by intestinal epithelial cells. Extensively heated ovomucoid that does not trigger anaphylaxis when given orally to sensitized mice was as efficacious as native ovomucoid in desensitizing mice.
CONCLUSIONS: OIT results in clinical protection against food-induced anaphylaxis through a novel mechanism that is localized to the intestinal mucosa and is associated with significant changes in small intestinal gene expression. Extensively heating egg allergen decreases allergenicity and increases safety while still retaining the ability to induce effective desensitization.
Authors:
Stephanie A Leonard; Gustavo Martos; Wei Wang; Anna Nowak-Węgrzyn; M Cecilia Berin
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-05-01
Journal Detail:
Title:  The Journal of allergy and clinical immunology     Volume:  129     ISSN:  1097-6825     ISO Abbreviation:  J. Allergy Clin. Immunol.     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-06-04     Completed Date:  2013-01-23     Revised Date:  2013-06-25    
Medline Journal Info:
Nlm Unique ID:  1275002     Medline TA:  J Allergy Clin Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1579-1587.e1     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
Affiliation:
Division of Pediatric Allergy and Immunology, Mount Sinai School of Medicine, New York, NY 10029, USA.
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MeSH Terms
Descriptor/Qualifier:
Administration, Oral
Allergens / administration & dosage*,  adverse effects,  immunology
Anaphylaxis / prevention & control,  therapy
Animals
Cytokines / immunology
Desensitization, Immunologic*
Disease Models, Animal
Egg White / adverse effects
Epitopes / immunology
Female
Food Hypersensitivity / genetics,  immunology,  therapy*
Gastric Mucosa / immunology*,  metabolism
Gene Expression Profiling
Immunoglobulin A / blood,  immunology
Immunoglobulin E / blood,  immunology
Intestinal Mucosa / immunology*,  metabolism
Mice
Mice, Inbred C3H
Ovomucin / administration & dosage,  adverse effects,  immunology
Protein Denaturation
Grant Support
ID/Acronym/Agency:
U19 AI044236/AI/NIAID NIH HHS; U19 AI044236-14/AI/NIAID NIH HHS; U19AI044236/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Allergens; 0/Cytokines; 0/Epitopes; 0/Immunoglobulin A; 37281-36-0/Ovomucin; 37341-29-0/Immunoglobulin E
Comments/Corrections

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