This project aims to study the immune responses to peanut allergen in those with a skin barrier defect with and without skin massage, specifically it aims to:

1. Establish if peanut allergen components can pass into human skin through regular massage using the peanut protein-containing extract.
2. Clarify whether this effect is amplified in those with an impaired skin barrier (AD and dry skin vs healthy controls).
3. Assess whether peanut protein components can be detected in interstitial skin fluid (ISF) using a suction device.
4. Test whether peanut protein components present in ISF are able to induce activation of basophils in blood of peanut allergic donors.
5. Assess whether the transcutaneous uptake of peanut protein can be reduced by the prior use of a barrier enhancing cream.

The study 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 under explored 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.

Inclusion Criteria:

• Adult healthy volunteers (50% of the cohort), and adults with dry skin and AD (fulfilling the refined Hanifin and Rajka criteria, 50% of the cohort).
• Willingness to apply the study intervention and to not use any other topical preparations over theforearms during the study period.

Exclusion Criteria:

• History of peanut allergy.
• Positive skin prick test to peanut (>0 mm).
• No regular consumption of peanut products.
• Widespread AD, in particular if this involves the test sites of the forearms.