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Investigation of the Association of Skin Barrier Structure and Function and the Development of Sensitisation to Food Allergens: A Prospective Birth Cohort Study

Institutions
University College Cork
Start date
2009
End date
2014
Objective

The project built upon data obtained from two linked Irish studies: SCOPE and BASELINE. In SCOPE, 3000 first-time mothers were recruited in early pregnancy with the aim of establishing biomarkers to help predict pregnancy outcomes. The BASELINE Study aimed to provide a detailed follow-up of the babies born from SCOPE, including collection and storage of umbilical cord blood, assessment of growth and health, collection of data on breast-feeding and weaning practices, and assessment of eczema status.

This project used established clinical protocols to determine the status of 1903 SCOPE/BASELINE babies with regards to FLG mutation, skin barrier function, and food allergen sensitisation and food allergy in the first 2 years of life. FLG mutation status was determined by analysis of cord blood of those antenatally recruited and saliva samples of those postnatally recruited. Skin barrier function was determined at 2 days, 2 months and 6 months of age by measuring the amount of water lost from the skin using a procedure known as Transepidermal Water Loss (TEWL). Food allergen sensitisation status was determined by Skin Prick Tests (SPTs) and blood tests for Specific Immunoglobulin E (SpIgE) antibodies at 2 years of age. Children whose parents reported adverse reactions to foods during the study underwent Double-Blind Placebo-Controlled Food Challenges (DBPCFCs) in order to determine their food allergic status.

The researchers anticipated that this prospective assessment would allow the genetic and functional status of skin barrier function to be determined and to identify whether these can be used as a means of categorising the children into groups according to their relative risk of developing food allergies.

More information

Background: A significant recent development in the science of food allergy has been recognition that food allergen sensitisation (the precursor to food allergy) could be acquired via routes of exposure other than dietary intake, notably through skin contact. However, whilst the importance of skin exposure in driving sensitisation to food allergens is suspected, and has been clearly demonstrated in animal models, it has not been established with certainty in humans.

The skin is constantly exposed to all types of allergens from the environment, and a protective outer layer known as the "skin barrier" prevents these from easily reaching the immune system. Loss-of-function mutations in the gene that produces the skin barrier maintenance protein, filaggrin (FLG), have been shown to be strongly associated with an increased risk of childhood eczema, and food allergy and eczema are known to be strongly associated in infants. The question is, therefore, whether a disrupted skin barrier, which may be genetically determined, facilitates the dermal exposure to food allergens during early life, and could thereby result in sensitisation and ultimately allergy to those foods developing. This study aimed to address this research question.

The study aimed to test two specific hypotheses. The primary hypothesis was that abnormal skin barrier function (with or without eczema) predates and predicts food allergen sensitisation, independent of other post-natal dietary and environmental factors. The secondary hypothesis was that any relationship between skin barrier function and food allergen sensitisation is driven by loss-of-function mutations in the FLG protein.

Funding Source
Food Standards Agency
Project source
View this project
Project number
FS231065 (T07060)
Categories
Natural Toxins
Risk Assessment, Management, and Communication