HDHL Preventing peanut allergy through improved understanding of the transcutaneous sensitisation route, novel food processing and skin care

Allergic diseases, including atopic dermatitis and food allergies affect many children across Europe. The immune responses to oral food allergens are well-established and controlled oral allergen exposure methods in early life have been developed that can prevent food allergies.

There is mounting evidence that early life cutaneous exposure to foods causes sensitisation, especially in the presence of dry skin and atopic dermatitis. Despite this, very little is known about how the cutaneous sensitisation to food allergies occurs.

This project aims to reduce the risk of peanut allergy development through the transcutaneous route by understanding the mechanisms through which this occurs, and by designing and testing novel prevention approaches, such as modification in the peanut manufacturing processes and the adaptation of skin care practices.

These aims will be addressed through integrated projects undertaken taken forward by leaders in their respective fields from the UK, Germany, and France. Each of these projects will be known separately as work-plans. Work-plan 1 will look into the effects of food processing upon the solubility of peanut protein and its components in oil and how this relates to the cutaneous exposure to peanut protein. Work-plan 2 will examine the effect of peanut protein skin contamination and skin appendage trapping. Work-plan 3 will study the immune system activation induced by massage and cutaneous peanut exposure. Work-plan 4 will use an interventional study approach with skin massage to study the immune responses to peanut allergen in those with a skin barrier defect. Work-plan 5 will examine the cutaneous immune responses to peanut allergen in those suffering of peanut allergy, and, work-plan 6 will translate the overall findings through working with an industrial peanut processing partner, patients and consumers.

The discoveries derived from the project will be shared with industry partners, charities, national and international food standards agencies to ensure stakeholder awareness and to encourage the findings of our work to be translated into improved public health measures with the hope to ultimately to reduce the burden of peanut allergy at the population level.

Our proposal aims to understand how peanut processing methods and peanut co-administration with oils, as is standard during the industrial processing of peanuts, influences the development of peanut allergy through the skin.

Cutaneous exposure of allergens is a crucial, but hitherto underexplored route of food sensitisation, that if understood could lead to the development of translatable strategies to prevent food allergy. Food processors require a greater understanding of how allergen exposure cause allergy so that they can adapt their processing methods to counteract these exposure processes. Furthermore, this proposed research aligns with on-going efforts across Europe to address the increasing problems associated with food allergy but it is unique in that it focuses on cutaneous allergen exposure, which is a field in desperate need of more systematic study.

The assembled team of investigators (from the UK, Germany and France) joined by a peanut industry partner (Levantine) and patient and consumer representatives will aim to address the following hypotheses:
Understanding the mechanisms by which:
> Peanut proteins pass into the skin via the appendages to trigger an immune response.
> Skin stretching that occurs during massage opens up the skin appendages allowing more peanut protein into the skin and leads to dendritic cell activation and induction of T helper 2 cell response.
> Co-administration of peanut proteins and an oil to the skin increases allergenicity.
> Skin barrier impairment and inflammation (AD) increases allergenicity.
Test novel approaches to peanut allergy prevention whereby:
> Modifications in peanut processing can reduce allergen exposure via the skin.
> Meticulous hand hygiene reduces skin contamination with peanut protein.
> Application of a barrier enhancing cream can strengthen the skin barrier, in particular in those with atopic dermatitis, and reduce the risk of transcutaneous sensitisation further.