Clinical efficacy and immune regulation with peanut oral immunotherapy

J Allergy Clin Immunol. 2009 Aug;124(2):292-300, 300.e1-97. doi: 10.1016/j.jaci.2009.05.022. Epub 2009 Jul 3.

Abstract

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 IgG(4) increased significantly. Serum factors inhibited IgE-peanut complex formation in an IgE-facilitated allergen binding assay. Secretion of IL-10, IL-5, IFN-gamma, and TNF-alpha 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.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adolescent
  • Allergens / administration & dosage*
  • Apoptosis*
  • Arachis / immunology*
  • Basophils / immunology
  • Child
  • Child, Preschool
  • Cytokines / biosynthesis
  • Cytokines / immunology
  • Desensitization, Immunologic / methods*
  • Down-Regulation
  • Female
  • Humans
  • Immunoglobulin E / blood
  • Immunoglobulin G / blood
  • Infant
  • Male
  • Microarray Analysis
  • Peanut Hypersensitivity / immunology*
  • Peanut Hypersensitivity / therapy*
  • Skin Tests
  • T-Lymphocytes, Regulatory / immunology
  • Treatment Outcome

Substances

  • Allergens
  • Cytokines
  • Immunoglobulin G
  • Immunoglobulin E