Epicutaneous immunotherapy for the treatment of peanut allergy in children and young adults

Jones, Stacie M.; Sicherer, Scott H.; Burks, A. Wesley; Leung, Donald Y.M.; Lindblad, Robert; Dawson, Peter; Henning, Alice K.; Berin, M. Cecilia; Chiang, David; Vickery, Brian P.; Pesek, Robbie D.; Cho, Christine B.; Davidson, Wendy F.; Plaut, Marshall; Sampson, Hugh A.; Wood, Robert A.

doi:10.1016/j.jaci.2016.08.017

Cited by 274 publications

(246 citation statements)

References 36 publications

(57 reference statements)

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“…In two multi-center trials conducted through CoFAR, we performed short-term stimulation of PBMCs with allergen for 6 or 18h, followed by flow cytometric identification of allergen-responsive T cells through detection of upregulation of the activation marker CD154 (CD40L). In samples analyzed as part of the primary analysis for one trial (Jones et al, 2017), we observed an overall failure rate of 31% in our regulatory T cell panel. Assay failure was due to low event count during acquisition, and these samples were characterized by altered scatter properties, and a low frequency of CD3 + CD4 + T cells.…”

Section: Introductionmentioning

confidence: 95%

Impact of granulocyte contamination on PBMC integrity of shipped blood samples: Implications for multi-center studies monitoring regulatory T cells

Agashe

Chiang

Grishin

et al. 2017

Journal of Immunological Methods

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In centralized immune monitoring for a multi-center allergen immunotherapy trial, we observed frequent loss of CD4+ T cell integrity following staining of cultured PBMCs with our regulatory T cell flow cytometry panel. Samples were marked by a loss of total cellular events, altered scatter properties, and reduced CD3+CD4+ events. This occurred only in samples that were stained with Foxp3 and were therefore treated with Foxp3 fixation-permeabilization buffer. We identified granulocyte contamination in samples associated with a loss of integrity, and went on to test the impact of granulocyte depletion on day-old blood samples. Granulocyte depletion prevented loss of cell integrity and CD3+CD4+ events, and reduced variability in detection of Foxp3+ cells. Addition of purified neutrophils back to PBMCs altered scatter properties and detection of CD4+ T cells. Implementation of a granulocyte depletion step in our standard operating protocols has reduced assay failure due to loss of sample integrity from 31% to 0%. Routine incorporation of a granulocyte depletion step during PBMC isolation is recommended prior to downstream immune monitoring in blood with next-day processing.

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Section: Introductionmentioning

confidence: 95%

Impact of granulocyte contamination on PBMC integrity of shipped blood samples: Implications for multi-center studies monitoring regulatory T cells

Agashe

Chiang

Grishin

et al. 2017

Journal of Immunological Methods

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“…The epicutaneous delivery of protein for immunotherapy is under investigation in patients with cow’s milk and peanut allergies [50–53, 54••]. The epicutaneous delivery system solubilizes the allergen by perspiration and disseminates it into the thickness of the stratum corneum [55].…”

Section: Potential Food Allergy Treatmentsmentioning

confidence: 99%

“…Epicutaneous delivery is non-invasive and may pose a lower risk for systemic reactions than other food allergen delivery approaches under study. Preliminary reports suggest that the epicutaneous antigen delivery for food allergy immunotherapy can lead to desensitization and appears to be more effective in children 6 to 11 years old than in older children and adults [53, 54••]. One important difference between the epicutaneous protocol and oral or sublingual approaches is that there is no dose escalation phase: the initial dose is the maintenance dose.…”

Section: Potential Food Allergy Treatmentsmentioning

confidence: 99%

“…One important difference between the epicutaneous protocol and oral or sublingual approaches is that there is no dose escalation phase: the initial dose is the maintenance dose. Doses are also lower than those used for other investigational therapies and, thus far, none of the trials reported serious adverse events [50–53]. The most frequent adverse events were localized erythema, eczema, pruritus, and/or urticaria at the site of application.…”

Section: Potential Food Allergy Treatmentsmentioning

confidence: 99%

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Food Allergy

Iweala

Choudhary

Commins

2018

Curr Gastroenterol Rep

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Purpose of Review The goal of this review is to present an updated summary of the natural history of major childhood and adult food allergies and report recent advances in potential treatments for food allergy. Recent Findings The most common childhood food allergies are typically outgrown by adolescence or adulthood. However, peanut/tree nut allergies appear to more commonly persist into adulthood. Adults can develop new IgE-mediated food allergies; the most common is oral allergy syndrome. There are multiple different approaches being tried as possible treatments for food allergy. Summary The prevalence of food allergy appears to be increasing but the varied approaches to treatment are being actively pursued such that an approved modality may not be too far in the future.

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“…These are immune-competent antigen-presenting cells that have the ability to initiate a regulatory T-cell response and communicate with regional lymph nodes. Daily application of EPIT patches containing 250 μg of peanut for 12 months in patients with peanut allergy has been shown to significantly raise the threshold dose for allergic reactions on food challenge [146,147]. The desensitization effect is not as marked as that of OIT, but the rate of adverse effects is minimal and mainly limited to local skin irritation where the EPIT patch has been applied [143].…”

Section: Food Allergen Immunotherapymentioning

confidence: 99%

Food Allergy Prevention and Treatment by Targeted Nutrition

Heine¹

2018

Ann Nutr Metab

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In view of the dramatic rise in the prevalence of food allergy globally, effective prevention strategies have become a public health priority. Several models have emerged around the etiology of food allergy, including the hygiene hypothesis, dual allergen exposure hypothesis, and vitamin D hypothesis. These form the basis for current and potential prevention strategies. Breastfeeding remains a key pillar of primary allergy prevention. Other nutritional interventions, including the use of whey-based, partially hydrolyzed formula in non-breastfed infants, also play an important role. In recent years, there has been a shift away from prolonged food allergen avoidance to the proactive allergen introduction from 4 months of age. This approach is supported by 2 pivotal randomized clinical trials showing that the early introduction of peanut and other food allergens significantly reduces the risk of food allergy. However, the implementation of this strategy at the population level still raises significant logistic problems, including patient selection and development of suitable food formats for young infants. Other prevention strategies, including vitamin D supplementation, are currently under evaluation. Maternal elimination diets during pregnancy and lactation are not recommended for allergy prevention. The treatment of food allergies has also seen major transformations. While strict allergen avoidance is still the key treatment principle, there is a greater focus on desensitization and tolerance induction by oral and epicutaneous immunotherapy. In addition, specialized hypoallergenic infant formulas for the treatment of infants with cow’s milk allergy have undergone reformulation, including the addition of lactose and probiotics in order to modulate the gut microbiome and early immune responses. Further research is needed to inform the most effective food allergy prevention strategies at the population level. In addition, the wider application of food allergen immunotherapy may provide better health outcomes and improved quality of life for families affected by food allergies.

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Epicutaneous immunotherapy for the treatment of peanut allergy in children and young adults

Cited by 274 publications

References 36 publications

Impact of granulocyte contamination on PBMC integrity of shipped blood samples: Implications for multi-center studies monitoring regulatory T cells

Impact of granulocyte contamination on PBMC integrity of shipped blood samples: Implications for multi-center studies monitoring regulatory T cells

Food Allergy

Food Allergy Prevention and Treatment by Targeted Nutrition

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