title: Peanut oral immunotherapy modifies IgE and IgG4 responses to major peanut allergens.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Pediatric Allergy and Immunology, Duke University School of Medicine, Durham, NC 27599, USA. bvickery@email.unc.edu
authors.forename: Brian P
authors.initials: BP
authors.lastname: Vickery
authors.forename: Jing
authors.initials: J
authors.lastname: Lin
authors.forename: Michael
authors.initials: M
authors.lastname: Kulis
authors.forename: Zhiyan
authors.initials: Z
authors.lastname: Fu
authors.forename: Pamela H
authors.initials: PH
authors.lastname: Steele
authors.forename: Stacie M
authors.initials: SM
authors.lastname: Jones
authors.forename: Amy M
authors.initials: AM
authors.lastname: Scurlock
authors.forename: Gustavo
authors.initials: G
authors.lastname: Gimenez
authors.forename: Ludmilla
authors.initials: L
authors.lastname: Bardina
authors.forename: Hugh A
authors.initials: HA
authors.lastname: Sampson
authors.forename: A Wesley
authors.initials: AW
authors.lastname: Burks
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology*; D000915:Antibody Affinity / Q000276:immunology; D010367:Arachis / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D003888:Desensitization, Immunologic; D000939:Epitopes / Q000276:immunology; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology*; D007223:Infant; D021183:Peanut Hypersensitivity / Q000276:immunology* / Q000628:therapy*
chemical_list: D000485:Allergens; D000939:Epitopes; D007074:Immunoglobulin G; D007073:Immunoglobulin E