Dataset Information

Allergen-Specific Immunotherapies for Food Allergy.

ABSTRACT: With rising prevalence of food allergy (FA), allergen-specific immunotherapy (AIT) for FA has become an active area of research in recent years. In AIT, incrementally increasing doses of inciting allergen are given with the goal to increase tolerance, initially through desensitization, which relies on regular exposure to allergen. With prolonged therapy in some subjects, AIT may induce sustained unresponsiveness, in which tolerance is retained after a period of allergen avoidance. Methods of AIT currently under study in humans include oral, sublingual, epicutaneous, and subcutaneous delivery of modified allergenic protein, as well as via DNA-based vaccines encoding allergen with lysosomal-associated membrane protein I. The balance of safety and efficacy varies by type of AIT, as well as by targeted allergen. Age, degree of sensitization, and other comorbidities may affect this balance within an individual patient. More recently, AIT with modified proteins or combined with immunomodulatory therapies has shown promise in making AIT safer and/or more effective. Though methods of AIT are neither currently advised by experts (oral immunotherapy [OIT]) nor widely available, AIT is likely to become a part of recommended management of FA in the coming years. Here, we review and compare methods of AIT currently under study in humans to prepare the practitioner for an exciting new phase in the care of food allergic patients in which improved tolerance to inciting foods will be a real possibility.

SUBMITTER: Feuille E

PROVIDER: S-EPMC5911438 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Allergen-Specific Immunotherapies for Food Allergy.

Feuille Elizabeth E Nowak-Wegrzyn Anna A

Allergy, asthma & immunology research 20180501 3

With rising prevalence of food allergy (FA), allergen-specific immunotherapy (AIT) for FA has become an active area of research in recent years. In AIT, incrementally increasing doses of inciting allergen are given with the goal to increase tolerance, initially through desensitization, which relies on regular exposure to allergen. With prolonged therapy in some subjects, AIT may induce sustained unresponsiveness, in which tolerance is retained after a period of allergen avoidance. Methods of AIT ...[more]

PMID: 29676066

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Project description:BackgroundHousehold endotoxin levels have been variably associated with risk for asthma and atopy.MethodsWe studied participants from the 2005-2006 National Health and Nutrition Examination Survey (NHANES, n = 6963), a large cohort representative of the US population (aged 1-84 years). We built logistic regression models to test for associations between house dust endotoxin and sensitization to specific foods (milk, egg, and peanut). To experimentally explore the detected epidemiologic associations, peripheral blood mononuclear cells (PBMCs) were collected from 21 children (aged 1-19 years) mono-food allergic (ie, sensitized and clinically reactive) to milk, egg, or peanut and nonallergic controls for stimulation with endotoxin and secreted cytokine measurement. For each food allergy, linear mixed-effects models were built to test the association between endotoxin stimulation and cytokine level.ResultsAmong NHANES subjects, the geometric mean household endotoxin level was 15.5 EU/mg (GSE 0.5). Prevalence of food allergen sensitization (sIgE ≥ 0.35 kUA /L) varied by food: milk 5.7%, egg 4.0%, and peanut 7.9%. In models adjusted for potential confounders (age, race, country of birth, total people per household, US region, and history of wheezing in the past year), household endotoxin level was associated with sensitization to milk (OR 1.7, 95% CI 1.2-2.1) and egg (OR 1.4, 95% CI 1.01-1.9), but not peanut (OR 0.98, 95% CI 0.8-1.2). Interferon-γ levels of endotoxin-stimulated PBMCs from children allergic to milk or egg, but not peanut, were significantly lower compared to controls in linear mixed-effects models adjusted for repeated measures, experimental variables, age, and inter-individual variability (P-values .007, .018, and .058, respectively).ConclusionHigher household endotoxin is associated with increased odds of milk and egg sensitization. Altered cytokine responsiveness to endotoxin is also observed in PBMCs from individuals with milk and egg allergy.

Project description:Background: Although adverse food reactions are commonly divided into immunoglobulin E (IgE) mediated food allergy (FA), and non-IgE FA, the current literature is providing support for the role of innate immune responses as an important component of non-IgE FA. Using a commercially available leukocyte activation (LA) assay, a recent quantitative study of total extracellular DNA released in cellular supernatants of human peripheral blood mononuclear cells exposed either to positive or negative tested foods demonstrated that leukocytes exposed to foods with positive LA test results showed higher DNA content than those exposed to foods with negative LA test results. In humans, the origin of DNA might be either the nucleus or the mitochondria. Analysis of emerging data from several laboratories, including our own, suggests that mitochondrial DNA induces inflammatory responses through induction of proinflammatory cytokines. Objective: This pilot study was designed primarily to convey the finding, and relevance of, mitochondrial DNA in the form of neutrophil extracellular traps (NET) as a new pathogenetic mechanism for innate immune-mediated non-IgE FA. Methods: The study population consisted of a total of six subjects, four in a major FA study group and two in a subgroup. Neutrophils were isolated and treated with food antigens that elicited positive and negative LA responses, and the released free DNA was analyzed for the cellular site of origin by using real-time polymerase chain reaction and for leukocyte calprotectin and S100 calcium-binding protein A12 (S100A12) proteins as markers of NETs. Results: We showed that cellular supernatants from neutrophils treated with foods that elicit positive LA responses can contain increased DNA levels of nuclear as well as mitochondrial origin. Supernatants from neutrophils treated with negative tested food (LA) responses did not induce the release of nuclear or mitochondrial DNA. Conclusion: Analysis of our data suggested that the induction of NETs that contain proinflammatory mitochondrial DNA may provide the critical link necessary for a better understanding of the pathogenesis of non-IgE-mediated FA. These discoveries may not only facilitate better diagnostic tests of FA but should also improve clinical management of allergic and other inflammatory diseases.

Dataset Information

Allergen-Specific Immunotherapies for Food Allergy.

Publications

Allergen-Specific Immunotherapies for Food Allergy.

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