Food allergies have become a world-wide public health problem, and allergy to peanuts is particularly problematic. In the U.S., ingestion of offending food allergens is the single most common cause of anaphylaxis seen in hospital emergency departments, and it is estimated that about 30,000 food-induced anaphylactic events are seen in U.S. emergency departments each year;sadly, about 200 of these events prove fatal. Either peanuts or tree nuts cause the majority of these deaths, and a recent survey in the U.S. found that 1.4% of the population is allergic to peanuts or tree nuts. Prior trials of immune desensitization using traditional and rush allergen protocols in patients with peanut allergy (PA) have shown partial rates of response but, unfortunately, have resulted in high rates of adverse reactions, including anaphylaxis. Recently, landmark studies by Dr. A. Wesley Burks and colleagues have shown success in desensitizing peanut-allergic children to peanut via an oral immunotherapy (OIT) protocol. The Stanford Alliance for Food Allergy Research (SAFAR, pronounced """"""""safer"""""""") is a multidisciplinary group whose goals are: 1) to develop and exploit state-of-the-art analytical methods, including advances in human immune monitoring, to improve understanding ofthe immune responses that give rise to food allergies and that underlie promising new approaches to treat this disorder, and 2) to contribute to the development and testing of improved approaches to diagnose, monitor, and treat subjects with food allergies. In this U19 application, we propose to conduct a large placebo-controlled, randomized, phase 2 clinical trial of OIT in children and adults with PA and to measure a broad range of cellular, serologic, and clinical findings in longitudinal samples from PA patients undergoing the trial, as well as from appropriate control subjects (namely, groups of placebo-treated PA subjects, healthy controls, and atopic controls without PA). These data will be used to determine how key immune system parameters are altered during OIT, and which are most predictive of the nature and durability of patient responses to this therapy. In addition, we seek to define immune monitoring parameters, including findings derived from analyses of basophil phenotype and function that can be rapidly performed In a clinical laboratory using very small amounts of blood, that could be used to predict the clinical reactivity to peanut in PA subjects, to improve the safety and efficacy of OIT protocols, and/or to tailor the OIT protocol to each individual subject. We hope that such work will help to achieve the goal of devising a safe and effective curative treatment of this severe disorder.

Public Health Relevance

Peanut allergy (PA) is an increasingly common disorder which can cause serious illness and death in children and adults. We will use Innovative approaches for DNA sequencing, immune monitoring, and data analysis to investigate factors responsible for PA and to improve our ability to manipulate the immune system to cure subjects of PA. We will also try to develop rapid blood tests that can be used to tailor treatment for each individual patient with PA in order to improve the safety and efficacy of such treatment.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
3U19AI104209-01S1
Application #
8699865
Study Section
Special Emphasis Panel (ZAI1-PA-I (J1))
Program Officer
Dong, Gang
Project Start
2013-07-01
Project End
2018-01-31
Budget Start
2013-07-01
Budget End
2014-01-31
Support Year
1
Fiscal Year
2013
Total Cost
$54,234
Indirect Cost
$19,690
Name
Stanford University
Department
Pathology
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
Ryan, John F; Hovde, Rachel; Glanville, Jacob et al. (2016) Successful immunotherapy induces previously unidentified allergen-specific CD4+ T-cell subsets. Proc Natl Acad Sci U S A 113:E1286-95
Levin, Mattias; King, Jasmine J; Glanville, Jacob et al. (2016) Persistence and evolution of allergen-specific IgE repertoires during subcutaneous specific immunotherapy. J Allergy Clin Immunol 137:1535-44
Yu, Wong; Freeland, Deborah M Hussey; Nadeau, Kari C (2016) Food allergy: immune mechanisms, diagnosis and immunotherapy. Nat Rev Immunol 16:751-765
Hussey Freeland, Deborah M; Fan-Minogue, Hua; Spergel, Jonathan M et al. (2016) Advances in food allergy oral immunotherapy: toward tolerance. Curr Opin Immunol 42:119-123
Gaudenzio, Nicolas; Sibilano, Riccardo; Marichal, Thomas et al. (2016) Different activation signals induce distinct mast cell degranulation strategies. J Clin Invest 126:3981-3998
Chinthrajah, R Sharon; Hernandez, Joseph D; Boyd, Scott D et al. (2016) Molecular and cellular mechanisms of food allergy and food tolerance. J Allergy Clin Immunol 137:984-97
Galli, Stephen J (2016) The Mast Cell-IgE Paradox: From Homeostasis to Anaphylaxis. Am J Pathol 186:212-24
Mukai, Kaori; Gaudenzio, Nicolas; Gupta, Sheena et al. (2016) Assessing basophil activation by using flow cytometry and mass cytometry in blood stored 24 hours before analysis. J Allergy Clin Immunol :
Pennington, Luke F; Tarchevskaya, Svetlana; Brigger, Daniel et al. (2016) Structural basis of omalizumab therapy and omalizumab-mediated IgE exchange. Nat Commun 7:11610
Hoh, Ramona A; Joshi, Shilpa A; Liu, Yi et al. (2016) Single B-cell deconvolution of peanut-specific antibody responses in allergic patients. J Allergy Clin Immunol 137:157-67

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