|KRONFEL, CHRISTINA - Oak Ridge Institute For Science And Education (ORISE)|
|SIMON, REYNA - Aimmune Therapeutics|
Submitted to: American Academy of Allergy Asthma and Immunology
Publication Type: Abstract Only
Publication Acceptance Date: 11/16/2015
Publication Date: N/A
Interpretive Summary: This project seeks to identify and assess changes in IgE and IgG4 epitopes of the major peanut allergens, Ara h 1, 2, 3, and 6, recognized by peanut allergic patients undergoing peanut oral immunotherapy in the US.
Technical Abstract: Rationale: Peanut oral immunotherapy (OIT) is a promising treatment to desensitize peanut allergic patients. Our aim was to identify and assess changes in IgE and IgG4 epitopes of the major peanut allergens, Ara h 1, 2, 3, and 6, recognized by peanut allergic patients undergoing peanut OIT in the US. Methods: Microarray slides containing synthetic overlapping 15-mer peptides offset by 5 aa of the major peanut allergens, Ara h 1, 2, 3, and 6, were incubated with sera from 27 peanut allergic patients from the US enrolled in Phase 2 and Phase 3 peanut OIT trials. The pre-trial and post-trial sera were collected between 5 months to a year apart, and were tested for IgE and IgG4 binding to the linear peptides using immunofluorescence. Results: IgE and IgG4 epitope maps for the four major peanut allergens were developed. While IgE binding patterns to the immunodominant epitopes (recognized by >70% of the sera) for each allergen did not seem to change much, there was significant changes in the intensity of the antibody binding for a majority of patient sera. Also, the peptide-specific IgE/IgG4 immunofluorescence ratios from pre-trial sera were higher than the post-trial sera. Conclusions: These results demonstrated that peanut OIT induces a shift in the IgE/IgG4 peptide-binding ratios in peanut allergic sera, but does not seem to alter the actual peptide binding patterns significantly after 1 year of OIT. This type of knowledge can be useful in the identification of peptide biomarkers that may indicate desensitization or tolerance of allergic individuals to peanut.