Protective Antibodies in Immunotherapy for Peanut Allergy

Key Words: Antibodies, B cells, Basophils, Allergy, Peanut

Food allergy is a growing public health concern, particularly in children. More than 1% of children in the United States have peanut allergy caused by allergy antibodies (IgE) putting them at risk for severe, life-threatening allergic responses to even minute exposures to peanut. Currently, the only available treatment is avoidance and emergent use of epinephrine.

Clinical trials of peanut oral immunotherapy (OIT) in which peanut allergic patients ingest incrementally increasing doses of peanut protein under clinical supervision, are currently underway. While many patients tolerate higher doses of peanut after OIT, only a subset develops long-lasting sustained responses. Recently, we discovered that these patients have a distinct peanut-specific antibody repertoire. We therefore hypothesize that patients with long-lasting tolerance after OIT develop protective antibodies against peanut that can prevent the interaction between peanut allergen with IgE and the consequent reaction from this interaction.

To test this, we will identify the rare peanut-specific B cells that produce these protective antibodies. We previously developed a highly specific tool, or a peanut-specific B cell tetramer, to select these cells from OIT-treated patients. We propose to now use this technique to identify protective antibodies and study how they function to neutralize the interaction with IgE. Identifying such antibodies may allow us to use them as a new therapy. Understanding how these protective antibodies develop in some patients after OIT will also help us design better immunotherapy strategies.