Allergic reactions to peanuts occur because susceptible individuals have an aberrant response to peanuts by producing a plasma protein, IgE, that binds to the high affinity receptor for IgE, FceRI, on mast cells and basophils. This IgE can be cross-linked by specific peanut proteins, called allergens, leading to a severe allergic reaction. Nine peanut proteins have been identified as allergens because they bind IgE from allergic individuals. Three of these, Ara h 1, Ara h 2, and Ara h 3 are called the major peanut allergens based on their ability to bind IgE on Western blots, to interact with IgE in RAST-inhibition assays, and to have measurable activity as assessed by in vitro and/or in vivo functional assays. Based on our work and the work of others, we now know that Ara h 2 is the most potent of these allergens. We have championed the concept of defining the major peanut allergens based on potency (not just activity) in functional assays that we have helped to develop. Our newest data examining the allergenicity of peanut extracts that have been specifically depleted of Ara h 2 demonstrate strongly that, for most severely peanut allergic patients, the activity of Ara h 2 does not account for the majority of the allergenic activity of peanuts. Using conventional chromatography combined with proteomics we have generated a relatively short list of new potential peanut allergens. We propose to extend our efforts to define quantitatively the major peanut allergens by combining our functional assays with the power of proteomics. In doing this we will define in molecular detail the peanut allergens most greatly responsible for mast cell activation in peanut allergic patients. We will test our in vitro findings in vivo using a mouse model of peanut allergy. This approach, in which we will definitively identify the most potent major allergens in peanuts has the potential to completely change our thinking as to which peanut allergens are the most important for allergic reactions in specific patients. Public Health Statement: Allergic reactions to peanuts are a major health problem for which current treatments are inadequate. Our knowledge of the molecular basis of peanut allergy is incomplete. This project is designed to use functional assays and proteomics to identify the molecules in peanuts that are most responsible for allergic reactions in susceptible persons.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI052164-08
Application #
8098190
Study Section
Special Emphasis Panel (ZRG1-HAI-G (09))
Program Officer
Plaut, Marshall
Project Start
2002-07-01
Project End
2012-06-30
Budget Start
2011-07-01
Budget End
2012-06-30
Support Year
8
Fiscal Year
2011
Total Cost
$388,835
Indirect Cost
Name
University of Colorado Denver
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
041096314
City
Aurora
State
CO
Country
United States
Zip Code
80045
Chen, Xueni; Negi, Surendra S; Liao, Sumei et al. (2016) Conformational IgE epitopes of peanut allergens Ara h 2 and Ara h 6. Clin Exp Allergy 46:1120-1128
Otsu, K; Guo, R; Dreskin, S C (2015) Epitope analysis of Ara h 2 and Ara h 6: characteristic patterns of IgE-binding fingerprints among individuals with similar clinical histories. Clin Exp Allergy 45:471-84
Bernard, Hervé; Guillon, Blanche; Drumare, Marie-Françoise et al. (2015) Allergenicity of peanut component Ara h 2: Contribution of conformational versus linear hydroxyproline-containing epitopes. J Allergy Clin Immunol 135:1267-74.e1-8
Koid, Audrey E; Chapman, Martin D; Hamilton, Robert G et al. (2014) Ara h 6 complements Ara h 2 as an important marker for IgE reactivity to peanut. J Agric Food Chem 62:206-13
Mills, K; Lay, J; Wu, W et al. (2014) Vitamin E, ?-tocopherol, diminishes ex vivo basophil response to dust mite allergen. Allergy 69:541-4
Chen, Xueni; Wang, Qian; El-Mezayen, Rabab et al. (2013) Ara h 2 and Ara h 6 have similar allergenic activity and are substantially redundant. Int Arch Allergy Immunol 160:251-8
Zhuang, Yonghua; Dreskin, Stephen C (2013) Redefining the major peanut allergens. Immunol Res 55:125-34
Kulis, M; Chen, X; Lew, J et al. (2012) The 2S albumin allergens of Arachis hypogaea, Ara h 2 and Ara h 6, are the major elicitors of anaphylaxis and can effectively desensitize peanut-allergic mice. Clin Exp Allergy 42:326-36
Zhuang, Yonghua; Durrani, Sandy; Hodges, Brittany D M et al. (2012) Expression of recombinant Ara h 6 in Pichia pastoris but not in Escherichia coli preserves allergic effector function and allows assessment of specific mutations. Mol Nutr Food Res 56:986-95
Martucci, Michael A; Dreskin, Stephen C (2011) Immunologic similarities between selected autoimmune diseases and peanut allergy: possible new therapeutic approaches. Curr Allergy Asthma Rep 11:334-9

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