Gideon Lack | Evelina Children's Hospital | London, United Kingdom
Evelina Children's Hospital | London, United Kingdom
ITN032AD
Completed
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.
Of the children who avoided peanut, 17% developed peanut allergy by the age of 5 years. Remarkably, only 3% of the children who were randomized to eating the peanut snack developed allergy by age 5. Therefore, in high-risk infants, sustained consumption of peanut beginning in the first 11 months of life was highly effective in preventing the development of peanut allergy.
This randomized parallel group study enrolled high risk infants. Half the children were randomised to early high dose consumption of peanut snack between age 4-11 months and the other half were randomized to complete dietary peanut avoidance. All 640 study participants were enrolled as of May 2009.
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 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.
Logan K, Bahnson HT, Ylescupidez A, Beyer K, Bellach J, Campbell DE, Craven J, Du Toit G, Clare Mills EN, Perkin MR, Roberts G, van Ree R, Lack G (2023). Early introduction of peanut reduces peanut allergy across risk groups in pooled and causal inference analyses. Allergy, 78 (5), 1307-1318.
Sever ML, Calatroni A, Roberts G, Du Toit G, Bahnson HT, Radulovic S, Larson D, Byron M, Santos AF, Huffaker MF, Wheatley LM, Lack G. (2023). Developing a Prediction Model for Determination of Peanut Allergy Status in the LEAP Studies. J Allergy Clin Immunol Pract, Epub ahead of print.
Baloh CH, Kanchan K, Shankar G, Nepom GT, Mathias RA, Perry JA. (2023). Omics-Oriented Research illustrated with the LEAP Study and the OASIS Bioinformatics Tool.. The Journal of Allergy and Clinical Immunology, 151 (2), 416-419.
Suprun M, Bahnson HT, Du Toit G, Lack G, Suarez-Farinas M, Sampson HA. (2023). In children with eczema, expansion of epitope-specific IgE is associated with peanut allergy at 5 years of age.. Allergy, 78 (2), 586-589.
Roberts, G. Bahnson. HT. Du Toit, G. O’Rourk, C. Sever, M, Brittain, E. Plaut, M. Lack, G. (2023). Defining the window of opportunity and the target populations to prevent peanut allergy. J Allergy Clin Immunol., 151 (5), 1329-1336.
DOI:
http://dx.doi.org/10.1016/j.jaci.2022.09.042,
PMID:
36521802
,
PMCID:
PMC10689252
,
PubMed,
ReprintKanchan K, Grinek S, Bahnson HT, Ruczinski I, Shankar G, Larson D, Du Toit G, Barnes KC, Sampson HA, Suarez-Farinas M, Lack G, Nepom GT, Cerosaletti K, Mathias RA (2022). HLA alleles and sustained peanut consumption promote IgG4 responses in subjects protected from peanut allergy. J Clin Invest, 132 (1).
Suarez-Farinas M, Suprun M, Kearney P, Getts R, Grishina G, Hayward C, Luta D, Porter A, Witmer M, Du Toit G, Lack G, Chinthrajah RS, Galli SJ, Nadeau K, Sampson H (2021). Accurate and reproducible diagnosis of peanut allergy using epitope mapping. Allergy, 76 (12), 3789-3797.
Suarez-Farinas M, Suprun M, Bahnson HT, Raghunathan R, Getts R, duToit G, Lack G, Sampson HA. (2021). Evolution of epitope-specific IgE and IgG 4 antibodies in children enrolled in the LEAP trial. The Journal of Allergy and Clinical Immunology, S0091-6749 (21).
DOI:
http://dx.doi.org/10.1016/j.jaci.2021.01.030,
PMID:
33592205
,
PMCID:
PMC8480440
,
PubMed,
ReprintTsilochristou O, Du Toit G, Sayre PH, Roberts G, Lawson K, Sever ML, Bahnson HT, Radulovic S, Basting M, Plaut M, Lack G, Immune Tolerance Network LEAP Study Team (2019). Association of Staphylococcus aureus colonization with food allergy occurs independently of eczema severity. The Journal of Allergy and Clinical Immunology.
Winters A, Bahnson HT, Ruczinski I, Boorgula MP, Malley C, Keramati AR, Chavan S, Larson D, Cerosaletti K, Sayre PH, Plaut M, Du Toit G, Lack G, Barnes KC, Nepom GT, Mathias RA, Immune Tolerance Network LEAP Study Team (2019). The MALT1 locus and Peanut Avoidance in the Risk for Peanut Allergy. J Allergy Clin Immunol, 19, 30279.
Sicherer SH, Sampson HA (2017). Food Allergy: A review and update on epidemiology, pathogenesis, diagnosis, prevention and management. J Allergy Clin Immunol.
Du Toit G, Plaut M, Lack G, Sampson H, Burks W, Akdis C (2017). Food Allergy: Update on Prevention and Tolerance. J Allergy Clin Immunol.
Greenhawt M, Fleischer DM, Chan ES, Venter C, Stukus D, Gupta R, Spergel JM (2017). LEAPing through the looking glass: secondary analysis of the effect of skin test size and age of introduction on peanut tolerance after early peanut introduction. Allergy, 72 (8), 1254-60.
Du Toit G, Sayre PH, Roberts G, Lawson K, Sever ML, Bahnson HT, Fisher HR, Feeney M, Radulovic S, Basting M, Plaut M, Lack G; Immune Tolerance Network LEAP Study Team (2017). The allergen-specificity of early peanut consumption and the impact on the development of allergic disease in the LEAP Study Cohort. J Allergy Clin Immunol, 141 (4), 1343-1353.
DOI:
http://dx.doi.org/10.1016/j.jaci.2017.09.034,
PMID:
29097103
,
PMCID:
PMC5889963
,
PubMed,
ReprintFeeney M, Du Toit G, Roberts G, Sayre PH, Lawson K, Bahnson HT, Sever ML, Radulovic S, Plaut M, Lack G, Immune Tolerance Network LEAP Study Team (2016). Impact of peanut consumption in the LEAP Study: Feasibility, growth, and nutrition . J Allergy Clin Immunol, pii: S0091-6749 (16), 30262-7.
DOI:
http://dx.doi.org/10.1016/j.jaci.2016.04.016,
PMID:
27297994
,
PMCID:
PMC5056823
,
PubMed,
ReprintDu Toit G, Sayre PH, Roberts G, Sever ML, Lawson K, Bahnson HT, Brough HA, Santos AF, Harris KM, Radulovic S, Basting M, Turcanu V, Plaut M, Lack G; Immune Tolerance Network LEAP-On Study Team (2016). Effect of Avoidance on Peanut Allergy after Early Peanut Consumption. N Engl J Med, 14 (374), 1435-43.
Du Toit G, Roberts G, Sayre PH, Bahnson HT, Radulovic S, Santos AF, Brough HA, Phippard D, Basting M, Feeney M, Turcanu V, Sever ML, Gomez Lorenzo M, Plaut M, Lack G; LEAP Study Team (2015). Randomized trial of peanut consumption in infants at risk for peanut allergy. N Engl J Med, 372 (9), 803-813.
DOI:
http://dx.doi.org/10.1056/NEJMoa1414850,
PMID:
25705822
,
PMCID:
PMC4416404
,
PubMed,
ReprintVickery BP, Scurlock AM, Kulis M, Steele PH, Kamilaris J, Berglund JP, Burk C, Hiegel A, Carlisle S, Christie L, Perry TT, Pesek RD, Sheikh S, Virkud Y, Smith PB, Shamji MH, Durham SR, Jones SM, Burks AW (2014). Sustained unresponsiveness to peanut in subjects who have completed peanut oral immunotherapy. J Allergy Clin Immunol, 133 (2), 468-75.
DOI:
http://dx.doi.org/10.1016/j.jaci.2013.11.007,
PMID:
24361082
,
PMCID:
PMC3960331
,
PubMed,
ReprintDu Toit G, Roberts G, Sayre PH, Plaut M, Bahnson HT, Mitchell H, Radulovic S, Chan S, Fox A, Turcanu V, Lack G (2012). Identifying infants at high risk of peanut allergy: The Learning Early About Peanut Allergy (LEAP) screening study. J Allergy Clin Immunol, 131 (1), 135-143.
Huffaker, M. F., Kanchan, K., Bahnson, H. T., Baloh, C., Lack, G., Nepom, G. T., & Mathias, R. A (2023). Incorporating genetics in identifying peanut allergy risk and tailoring allergen immunotherapy: A perspective on the genetic findings from the LEAP trial. Journal of Allergy and Clinical Immunology, Epub ahead of print.
Fisher HR, Du Toit G, Bahnson HT, Lack G (2018). The challenges of preventing food allergy: Lessons learned from LEAP and EAT. Ann Allergy Asthma Immunol, 121 (3), 313-319.
Renz H, Allen KJ, Sicherer SH, Sampson HA, Lack G, Beyer K, Oettgen HC (2018). Food allergy. Nat Rev Dis Primers, 4 (4), 17098.
Lawson K, Bahnson HT, Sever M, Du Toit G, Lack G, Brittain E, Keet C, Greenhawt M, Fleischer D, Chan ES, Venter C, Stukus D, Gupta R, Spergel J (2017). Letter of response to Greenhawt et al. 'LEAPing Through the Looking Glass: Secondary Analysis of the Effect of Skin Test Size and Age of Introduction on Peanut Tolerance after Early Peanut Introduction'. Allergy, 72 (8), 1267-71.
Du Toit G, Lack G, Tsakok T, Lack S (2016). Prevention of food allergy. J Allergy Clin Immunol, 137 (4), 998-1010.
Bahnson HT, Du Toit G, Lack G (2017). Statistical Considerations of Food Allergy Prevention Studies. J Allergy Clin Immunol Pract, 5 (2), 274-82.
Wang J, Lack G (2017). Food Allergy: Unmet Needs and New Perspectives. J Allergy Clin Immunol Pract, 5 (2), 295.
