Promoting Tolerance to Peanut in High-Risk Children (LEAP)
Evelina Children's Hospital | London, United Kingdom
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, and 2. Early oral exposure may be required to prevent the development of peanut allergy through oral tolerance induction. UK and US guidelines had previously discouraged oral exposure during pregnancy, breastfeeding and infancy. These guidelines may have promoted 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 enroll high risk infants. Half the children will be randomised to early high dose consumption of peanut snack between age 4-11 months and the other half will be randomized to complete dietary peanut avoidance. All 640 study participants were enrolled as of May 2009. The total study will last 7 years with study closure anticipated in 2014. 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.” Peptide specific IgE and IgG epitopes in the different tolerant and allergic states will also be studied. This 7 year study will include a 2 year enrollment 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.
Du Toit G, Roberts G, Sayre PH, Plaut M, Bahnson HT, Mitchell H, Radulovic S, Chan S, Fox A, Turcanu V, Lack G. Identifying infants at high risk of peanut allergy: The Learning Early About Peanut Allergy (LEAP) screening studyJ Allergy Clin Immunol 2013 Jan; 131(1):135-143.e1-12. PMID: 23174658.. [PubMed] [Reprint]
Sayre P, Broide D, Seyfert-Margolis V, Roberts G, Du Toit G, Turcanu V, Fisher HR, Nirenstein L, Radulovic S, Stephens A, Nasser N, Murphy S, The Immune Tolerance Network ITN032AD Study Group, Lack G. Roberts - AAAAI 2010. (Abstract #363) 2010 AAAAI Annual Meeting, New Orleans, LA, February 26 - March 2, 2010.
Du Toit G, Roberts G, Sayre P, Turcanu V, Fisher HR, Broide D, Nirenstein L, Radulovic S, Stephens A, Seyfert-Margolis V, Nasser N, Murphy S, The Immune Tolerance Network ITN032AD Study Group, Lack G. DuToit - AAAAI 2010. (Abstract #84) 2010 AAAAI Annual Meeting, New Orleans, LA, February 26 - March 2, 2010.