Clinical efficacy and immune regulation with peanut oral immunotherapy

Received 19 November 2008; received in revised form 28 April 2009; accepted 12 May 2009. published online 06 July 2009.

Background

Oral immunotherapy (OIT) has been thought to induce clinical desensitization to allergenic foods, but trials coupling the clinical response and immunologic effects of peanut OIT have not been reported.

Objective

The study objective was to investigate the clinical efficacy and immunologic changes associated with OIT.

Methods

Children with peanut allergy underwent an OIT protocol including initial day escalation, buildup, and maintenance phases, and then oral food challenge. Clinical response and immunologic changes were evaluated.

Results

Of 29 subjects who completed the protocol, 27 ingested 3.9 g peanut protein during food challenge. Most symptoms noted during OIT resolved spontaneously or with antihistamines. By 6 months, titrated skin prick tests and activation of basophils significantly declined. Peanut-specific IgE decreased by 12 to 18 months, whereas IgG4 increased significantly. Serum factors inhibited IgE–peanut complex formation in an IgE-facilitated allergen binding assay. Secretion of IL-10, IL-5, IFN-γ, and TNF-α from PBMCs increased over a period of 6 to 12 months. Peanut-specific forkhead box protein 3 T cells increased until 12 months and decreased thereafter. In addition, T-cell microarrays showed downregulation of genes in apoptotic pathways.

Conclusion

Oral immunotherapy induces clinical desensitization to peanut, with significant longer-term humoral and cellular changes. Microarray data suggest a novel role for apoptosis in OIT.

Key words: Peanut hypersensitivity, immunotherapy, immune tolerance, apoptosis, IgE, IgG, IL-5, IL-10

Abbreviations used: FAB, Facilitated allergen binding, FoxP3, Forkhead box protein 3, MIP, Macrophage inflammatory protein, OFC, Oral food challenge, OIT, Oral immunotherapy, PBMC, Peripheral blood mononuclear cell, SPT, Skin prick test, Treg, Regulatory T cell

a Department of Pediatrics, University of Arkansas for Medical Sciences and Arkansas Children's Hospital, Little Rock, Ark

b Department of Pediatrics, Duke University Medical Center, Durham, NC

c Department of Pediatrics, Mount Sinai Medical Center, New York, NY

d Imperial College, London, United Kingdom

Reprint requests: A. Wesley Burks, MD, Duke University Medical Center, Box 2644, Durham, NC 27710.

Supported by the Food Allergy and Anaphylaxis Network, the Gerber Foundation, National Institutes of Health grant 1R01-AI068074-01A1, the Arkansas Biosciences Institute, the Dorothy and Frank Robins Family, the Food Allergy Project, and Clinical and Translational Science Award 5M01-R000030-45.

Disclosure of potential conflict of interest: A. W. Burks is a consultant for ActoGeniX NV, Intelliject, McNeil Nutritionals, and Novartis; is a minority stockholder of Allertein Therapeutics and MastCell Pharmaceuticals, Inc; is on the advisory board for The Dannon Company, Inc.; is on the expert panel for Nutricia; has received research support from the National Institutes of Health, the Food Allergy and Anaphylaxis Network, and the Wallace Research Foundation; has served as an expert witness regarding food allergy; is on the Medical Board of Directors for the Food Allergy and Anaphylaxis Network; is on the Dermatological Allergy Committee for American College of Allergy, Asthma & Immunology; is a study section member of the National Institutes of Health Hypersensitivity, Autoimmunity, and Immunodeficiency; and is on the Journal of Allergy and Clinical Immunology review board. S. M. Jones is a consultant and board member for the Food Allergy and Anaphylaxis Network and has received research support from the National Institutes of Health, the Food Allergy and Anaphylaxis Network, the National Peanut Board, Mead Johnson, and Dyax Corp. J. L. Roberts has received research support from the National Institutes of Health. A. M. Scurlock has received research support from the National Institutes of Health/National Institute of Allergy and Infectious Diseases and Genocea Biosciences. T. T. Perry has received research support from the National Institutes of Health/National Institute of Allergy and Infectious Diseases, the Robert Wood Johnson Foundation, and Arkansas Biosciences Institute, Lyon. M. Kulis has received research support from the Food Allergy Initiative. W. G. Shreffler has received research support from the Food Allergy and Anaphylaxis Network. S. Durham has provided consultancy and lectures for and has received research support from GlaxoSmithKline and ALK-Abelló. B. P. Vickery has received research support from the National Institutes of Health and Ception Therapeutics. X. Zhong has received research support from the National Institutes of Health, the American Cancer Society, and the American Heart Association. The rest of the authors have declared that they have no conflict of interest.

PII: S0091-6749(09)00813-6

doi:10.1016/j.jaci.2009.05.022

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