Protective Antibodies in Immunotherapy for Peanut Allergy
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.