Peanut allergy (PA) is a potentially fatal disorder In need of improved methods for diagnosis, clinical monitoring, and treatment. Basophils, the least common blood granulocyte, have been implicated as Important contributors to the pathology of PA and peanut-induced anaphylaxis. Certain cell surface phenotypic features can help to Identify basophils which have been activated by allergic mechanisms in vivo or in vitro. In this project, we seek to determine whether the phenotype and function of blood basophils can be used as part of an approach to predict the severity of clinical reactivity to peanut In individual subjects with PA, to improve the safety and efficacy of an oral Immunotherapy (OIT) protocol to treat PA, and/or to customize the OIT protocol to each individual peanut allergic subject.
In Aim 1 of this project, we will employ detailed immuophenotyping approaches to monitor the phenotype and activation status of basophils in the peripheral blood of pediatric and adult subjects with PA, as measured at baseline before their enrollment in a phase 2 clinical trial of OIT for PA (Project 1 of this U19 application) and at multiple intervals during the course of OIT. This work will test the hypothesis that the expression of activation and cell surface markers in the blood basophils of PA patients correlates with their acute clinical reactivity to peanut allergen before and during OIT and can be used to monitor the development, success, and durability of tolerance induced by OIT.
In Aim 2, we will perform in vitro studies of human basophil phenotype and function (i.e., basophil activation tests [BATs]), to measure the responses of such basophils to challenge with offending (peanut) vs. irrelevant allergens ex vivo. This work will test the hypothesis that the magnitude of peanut allergen-induced changes in the phenotype (e.g., surface expression ofCD20Sc) or function (e.g., secretion of mediators) of blood basophils of PA patients correlates with the reduction in clinical evidence of peanut allergen sensitivity over the course of OIT. One of our key goals in this work is to develop innovative, rapid, and reliable methods to monitor basophil phenotype and function that can be used clinically for such purposes as predicting a subject's clinical sensitivity to peanut, predicting the clinical outcome of OIT, customizing the OIT protocol optimally for individual subjects, and/or monitoring the development, effectiveness, or durability of OIT.

Public Health Relevance

Basophils are white blood cells that release products which contribute to the pathology of peanut allergy (PA). We will evaluate whether rapidly testing the blood basophils of patients with PA, using very small amounts of blood, can be used to make the immunotherapy of PA safer and more effective, and can permit the Individual tailoring of such immunotherapy based on the analysis of basophils of individual subjects.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
1U19AI104209-01
Application #
8468489
Study Section
Special Emphasis Panel (ZAI1-PA-I (J1))
Project Start
Project End
Budget Start
2013-02-01
Budget End
2014-01-31
Support Year
1
Fiscal Year
2013
Total Cost
$417,807
Indirect Cost
$151,688
Name
Stanford University
Department
Type
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
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Starkl, Philipp; Marichal, Thomas; Galli, Stephen J (2013) PLA2G3 promotes mast cell maturation and function. Nat Immunol 14:527-9