Peanut oral immunotherapy modifies IgE and IgG4 responses to major peanut allergens

J Allergy Clin Immunol. 2013 Jan;131(1):128-34.e1-3. doi: 10.1016/j.jaci.2012.10.048. Epub 2012 Nov 27.

Abstract

Background: Patients with peanut allergy have highly stable pathologic antibody repertoires to the immunodominant B-cell epitopes of the major peanut allergens Ara h 1 to 3.

Objective: We used a peptide microarray technique to analyze the effect of treatment with peanut oral immunotherapy (OIT) on such repertoires.

Methods: Measurements of total peanut-specific IgE (psIgE) and peanut-specific IgG(4) (psIgG(4)) were made with CAP-FEIA. We analyzed sera from 22 patients with OIT and 6 control subjects and measured serum specific IgE and IgG(4) binding to epitopes of Ara h 1 to 3 using a high-throughput peptide microarray technique. Antibody affinity was measured by using a competitive peptide microarray, as previously described.

Results: At baseline, psIgE and psIgG(4) diversity was similar between patients and control subjects, and there was broad variation in epitope recognition. After a median of 41 months of OIT, polyclonal psIgG(4) levels increased from a median of 0.3 μg/mL (interquartile range [25% to 75%], 0.1-0.43 μg/mL) at baseline to 10.5 μg/mL (interquartile range [25% to 75%], 3.95-45.48 μg/mL; P < .0001) and included de novo specificities. psIgE levels were reduced from a median baseline of 85.45 kU(A)/L (23.05-101.0 kU(A)/L) to 7.75 kU(A)/L (2.58-30.55 kU(A)/L, P < .0001). Affinity was unaffected. Although the psIgE repertoire contracted in most OIT-treated patients, several subjects generated new IgE specificities, even as the total psIgE level decreased. Global epitope-specific shifts from IgE to IgG(4) binding occurred, including at an informative epitope of Ara h 2.

Conclusion: OIT differentially alters Ara h 1 to 3 binding patterns. These changes are variable between patients, are not observed in control subjects, and include a progressive polyclonal increase in IgG(4) levels, with concurrent reduction in IgE amount and diversity.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Oral
  • Adolescent
  • Allergens / administration & dosage
  • Allergens / immunology*
  • Antibody Affinity / immunology
  • Arachis / immunology*
  • Child
  • Child, Preschool
  • Desensitization, Immunologic*
  • Epitopes / immunology
  • Humans
  • Immunoglobulin E / blood
  • Immunoglobulin E / immunology*
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology*
  • Infant
  • Peanut Hypersensitivity / immunology*
  • Peanut Hypersensitivity / therapy*

Substances

  • Allergens
  • Epitopes
  • Immunoglobulin G
  • Immunoglobulin E