Induction of tolerance through early introduction of peanut in ‘high risk’ children
(in development)

Principal Investigator:
Gideon Lack, Imperial College, London, UK

Abstract | Investigators | Background

Abstract

The prevalence of peanut allergy has doubled over the past 10 years in countries that advocate avoidance of peanuts during pregnancy, lactation and infancy. Peanut allergy now affects approximately 1.5% of young children. There are 2 main explanations for this failure to prevent peanut allergies through avoidance measures; 1. Sensitisation to food allergens may not occur through oral exposure, but rather through other routes such as topical cutaneous exposure; 2. Early oral exposure may be required to prevent the development of peanut allergy through oral tolerance induction. Paradoxically, UK and US guidelines may promote allergic sensitisation by creating a situation where there is environmental cutaneous exposure in the absence of early oral tolerance induction: this imbalance in the routes of allergen presentation may favour the development of allergic sensitisation.

The primary aim of our study is to determine which is the best strategy for reducing peanut allergy, early high dose consumption of peanut protein or avoidance. Secondary aims are to compare the development of sensitisation to peanuts, the development of tree nut allergy at age 5, sensitisation to control allergens (house dust mite and egg) and immunological assays.

This randomized parallel group study will enrol high risk infants. Half the children will be randomised to early high dose consumption of peanut snack between age 4-8 months and the other half will be randomized to complete dietary peanut avoidance. The total study will last 7 years: We intend to freeze serum and cells in all children at four different time points during the course of the study.

Immunological assays will focus on alterations in the function of peanut-specific T cells (cytokine production, precursor cell frequency), the development of regulatory T cells subsets, the importance of IgE dependent facilitated antigen presentation and the development of IgG4 as a “blocking antibody”. Peptidespecific IgE and IgG epitopes in the different tolerant and allergic states will also be studied. This 7 year study will include a 2 year enrolment period and 5 years intervention. This will allow us to address both the clinical and immunological specificity of oral tolerance induction, study the underlying mechanisms of oral tolerance and provide a new strategy to prevent allergic disease.

Participating Investigators

	Gideon Lack, Imperial College, London, UK
	George Du Toit, Imperial College, London, UK
	Hugh Sampson, Mt Sinai School of Medicine, NY
	Douglas Robinson, Imperial College, London, UK
	Stephen Durham, Imperial College, London, UK
	Victor Turcanu, Imperial College, London, UK
	Graham Roberts, University of Southampton, UK

Background Articles

	The development and prediction of atopy in high-risk children: Follow-up at age seven years in a prospective randomized study of combined maternal and infant food allergen avoidance - J Allergy Clin Immunol [Abstract]
	Factors Associated with the Development of Peanut Allergy in Childhood - NEJM [Abstract]
	Characterization of lymphocyte responses to peanuts in normal children, peanut-allergic children, and allergic children who acquired tolerance to peanuts - J Clin Invest [Full Text]