Evolution of epitope-specific IgE and IgG 4 antibodies in children enrolled in the LEAP trial

J Allergy Clin Immunol. 2021 Sep;148(3):835-842. doi: 10.1016/j.jaci.2021.01.030. Epub 2021 Feb 13.


Background: In the LEAP (Learning Early About Peanut Allergy) trial, early consumption of peanut in high-risk infants was found to decrease the rate of peanut allergy at 5 years of age. Sequential epitope-specific (ses-)IgE is a promising biomarker of clinical peanut reactivity.

Objective: We sought to compare the evolution of ses-IgE and ses-IgG4 in children who developed (or not) peanut allergy and to evaluate the immunomodulatory effects of early peanut consumption on these antibodies.

Methods: Sera from 341 children (LEAP cohort) were assayed at baseline, 1, 2.5, and 5 years of age, with allergy status determined by oral food challenge at 5 years. A bead-based epitope assay was used to quantitate ses-IgE and ses-IgG4 to 64 sequential epitopes from Ara h 1 to Ara h 3 and was analyzed using linear mixed-effect models.

Results: In children avoiding peanut who became peanut allergic, the bulk of peanut ses-IgE did not develop until after 2.5 years. Minimal increases of ses-IgE occurred after 1 year in consumers, but not to the same epitopes as those in children developing peanut allergy. No major changes in ses-IgE were seen in nonallergic or sensitized children. IgE in sensitized consumers was detected against peanut proteins. ses-IgG4 increased over time in most children regardless of consumption or allergy status.

Conclusions: Early peanut consumption in infants at high risk of developing peanut allergy appears to divert the immunologic response to a presumably "protective" effect. In general, consumers tend to generate ses-IgG4 earlier and in greater quantities than nonconsumers do, whereas only avoiders tend to generate significant quantities of ses-IgE.

Keywords: IgE; IgG(4); Peanut allergy; antibody; bead-based epitope assay; biomarkers; sequential epitope.

Publication types

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

MeSH terms

  • Allergens / immunology
  • Antigens, Plant / immunology
  • Arachis / immunology
  • Child, Preschool
  • Epitopes / immunology*
  • Female
  • Humans
  • Immunoglobulin E / immunology*
  • Immunoglobulin G / immunology*
  • Immunomodulation
  • Infant
  • Male
  • Membrane Proteins / immunology
  • Peanut Hypersensitivity / immunology*
  • Plant Proteins / immunology


  • Allergens
  • Antigens, Plant
  • Ara h 1 protein, Arachis hypogaea
  • Ara h 3 allergen, Arachis hypogea
  • Epitopes
  • Immunoglobulin G
  • Membrane Proteins
  • Plant Proteins
  • Immunoglobulin E