Hostname: page-component-586b7cd67f-tf8b9 Total loading time: 0 Render date: 2024-11-29T05:50:52.892Z Has data issue: false hasContentIssue false
  • English
  • Français

The peanut allergy epidemic: allergen molecular characterisation and prospects for specific therapy

Published online by Cambridge University Press:  09 January 2007

Maria P. de Leon ,
Jennifer M. Rolland  and
Robyn E. O'Hehir
Maria P. de Leon
Affiliation:
Department of Immunology, Monash University, Melbourne, Victoria 3004, Australia.
Jennifer M. Rolland
Affiliation:
Department of Immunology, Monash University, Melbourne, Victoria 3004, Australia.
Robyn E. O'Hehir*
Affiliation:
Department of Immunology, Monash University, Melbourne, Victoria 3004, Australia. Department of Allergy, Immunology and Respiratory Medicine, Alfred Hospital, Melbourne, Victoria 3004, Australia.
*
*Corresponding author: Robyn E. O'Hehir, Department of Allergy, Immunology and Respiratory Medicine, Alfred Hospital, Commercial Road, Melbourne, Victoria 3004, Australia. Tel: +61 3 9276 2251; Fax: +61 3 9207 1692; E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Peanut (Arachis hypogaea) allergy is a major cause of food-induced anaphylaxis, with increasing prevalence worldwide. To date, there is no cure for peanut allergy, and, unlike many other food allergies, it usually persists through to adulthood. Prevention of exposure to peanuts is managed through strict avoidance, which can be compromised by the frequent use of peanuts and peanut products in food preparations. Conventional subcutaneous-injection allergen immunotherapy using crude peanut extract is not a recommended treatment because of the risk of severe side effects, largely as a result of specific IgE antibodies. Consequently, there is an urgent need to develop a suitable peanut allergen preparation that can induce specific clinical and immunological tolerance to peanuts in allergic individuals without adverse side effects. This requires detailed molecular and immunological characterisation of the allergenic components of peanut. This article reviews current knowledge on clinically relevant peanut allergens, in particular Ara h 1, Ara h 2 and Ara h 3, together with options for T-cell-reactive but non-IgE-binding allergen variants for specific immunotherapeutic strategies. These include T-cell-epitope peptide and hypoallergenic mutant vaccines. Alternative routes of administration such as sublingual are also considered, and appropriate adjuvants for delivering effective treatments at these sites examined.

Type
Research Article
Information
Expert Reviews in Molecular Medicine , Volume 9 , Issue 1 , January 2007 , pp. 1 - 18
Copyright
Copyright © Cambridge University Press 2007

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

References

1Sicherer, S.H., Munoz-Furlong, A. and Sampson, H.A. (2003) Prevalence of peanut and tree nut allergy in the United States determined by means of a random digit dial telephone survey: a 5-year follow-up study. J Allergy Clin Immunol 112, 1203-1207CrossRefGoogle ScholarPubMed
2Grundy, J. et al. (2002) Rising prevalence of allergy to peanut in children: data from 2 sequential cohorts. J Allergy Clin Immunol 110, 784-789CrossRefGoogle ScholarPubMed
3Sampson, H.A., Mendelson, L. and Rosen, J.P. (1992) Fatal and near-fatal anaphylactic reactions to food in children and adolescents. N Engl J Med 327, 380-384CrossRefGoogle ScholarPubMed
4Bock, S.A., Munoz-Furlong, A. and Sampson, H.A. (2001) Fatalities due to anaphylactic reactions to foods. J Allergy Clin Immunol 107, 191-193CrossRefGoogle ScholarPubMed
5Lack, G. et al. (2003) Factors associated with the development of peanut allergy in childhood. N Engl J Med 348, 977-985CrossRefGoogle ScholarPubMed
6Kaufman, H.S. (1971) Allergy in the newborn: skin test reactions confirmed by the Prausnitz-Kustner test at birth. Clin Allergy 1, 363-367CrossRefGoogle ScholarPubMed
7Vadas, P. et al. (2001) Detection of peanut allergens in breast milk of lactating women. JAMA 285, 1746-1748CrossRefGoogle ScholarPubMed
8Sampson, H.A. (2002) Peanut allergy. N Engl J Med 346, 1294-1299CrossRefGoogle ScholarPubMed
9Bock, S.A. and Atkins, F.M. (1989) The natural history of peanut allergy. J Allergy Clin Immunol 83, 900-904CrossRefGoogle ScholarPubMed
10Skolnick, H.S. et al. (2001) The natural history of peanut allergy. J Allergy Clin Immunol 107, 367-374CrossRefGoogle ScholarPubMed
11Prioult, G. and Nagler-Anderson, C. (2005) Mucosal immunity and allergic responses: lack of regulation and/or lack of microbial stimulation? Immunol Rev 206, 204-218CrossRefGoogle ScholarPubMed
12Strobel, S. and Mowat, A.M. (2006) Oral tolerance and allergic responses to food proteins. Curr Opin Allergy Clin Immunol 6, 207-213CrossRefGoogle ScholarPubMed
13Mosmann, T.R. et al. (1986) Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol 136, 2348-2357CrossRefGoogle ScholarPubMed
14Gleich, G.J. (2000) Mechanisms of eosinophil-associated inflammation. J Allergy Clin Immunol 105, 651-663CrossRefGoogle ScholarPubMed
15Hourihane, J.O. et al. (1997) Randomised, double blind, crossover challenge study of allergenicity of peanut oils in subjects allergic to peanuts. BMJ 314, 1084-1088CrossRefGoogle ScholarPubMed
16Hoffmann, D.R. and Collins-Williams, C. (1994) Cold pressed peanut oils may contain peanut allergen. J Allergy Clin Immunol 93, 801-802CrossRefGoogle Scholar
17Secrist, H. et al. (1993) Allergen immunotherapy decreases interleukin 4 production in CD4+T cells from allergic individuals. J Exp Med 178, 2123-2130CrossRefGoogle ScholarPubMed
18Gardner, L.M. et al. (2004) Induction of T ‘regulatory’ cells by standardized house dust mite immunotherapy: an increase in CD4+ CD25+ interleukin-10+ T cells expressing peripheral tissue trafficking markers. Clin Exp Allergy 34, 1209-1219CrossRefGoogle ScholarPubMed
19Bellinghausen, I. et al. (1997) Insect venom immunotherapy induces interleukin-10 production and a Th2-to-Th1 shift, and changes surface marker expression in venom-allergic subjects. Eur J Immunol 27, 1131-1139CrossRefGoogle Scholar
20Jutel, M. et al. (2003) IL-10 and TGF-beta cooperate in the regulatory T cell response to mucosal allergens in normal immunity and specific immunotherapy. Eur J Immunol 33, 1205-1214CrossRefGoogle ScholarPubMed
21Flicker, S. and Valenta, R. (2003) Renaissance of the blocking antibody concept in type I allergy. Int Arch Allergy Immunol 132, 13-24CrossRefGoogle ScholarPubMed
22Patriarca, G. et al. (2006) Oral rush desensitization in peanut allergy: a case report. Dig Dis Sci 51, 471-473CrossRefGoogle ScholarPubMed
23Oppenheimer, J.J. et al. (1992) Treatment of peanut allergy with rush immunotherapy. J Allergy Clin Immunol 90, 256-262CrossRefGoogle ScholarPubMed
24Burks, A.W. et al. (1991) Identification of a major peanut allergen, Ara h I, in patients with atopic dermatitis and positive peanut challenges. J Allergy Clin Immunol 88, 172-179CrossRefGoogle Scholar
25Burks, A.W. et al. (1992) Identification and characterization of a second major peanut allergen, Ara h II, with use of the sera of patients with atopic dermatitis and positive peanut challenge. J Allergy Clin Immunol 90, 962-969CrossRefGoogle ScholarPubMed
26Burks, A.W. et al. (1995) Recombinant peanut allergen Ara h I expression and IgE binding in patients with peanut hypersensitivity. J Clin Invest 96, 1715-1721CrossRefGoogle ScholarPubMed
27Rabjohn, P. et al. (1999) Molecular cloning and epitope analysis of the peanut allergen Ara h 3. J Clin Invest 103, 535-542CrossRefGoogle ScholarPubMed
28Restani, P. et al. (2005) Identification of the basic subunit of Ara h 3 as the major allergen in a group of children allergic to peanuts. Ann Allergy Asthma Immunol 94, 262-266CrossRefGoogle Scholar
29Kleber-Janke, T. et al. (1999) Selective cloning of peanut allergens, including profilin and 2S albumins, by phage display technology. Int Arch Allergy Immunol 119, 265-274CrossRefGoogle ScholarPubMed
30Mittag, D. et al. (2004) Ara h 8, a Bet v 1-homologous allergen from peanut, is a major allergen in patients with combined birch pollen and peanut allergy. J Allergy Clin Immunol 114, 1410-1417CrossRefGoogle Scholar
31Breiteneder, H. and Ebner, C. (2000) Molecular and biochemical classification of plant-derived food allergens. J Allergy Clin Immunol 106, 27-36CrossRefGoogle ScholarPubMed
32Koppelman, S.J. et al. (1999) Heat-induced conformational changes of Ara h 1, a major peanut allergen, do not affect its allergenic properties. J Biol Chem 274, 4770-4777CrossRefGoogle Scholar
33Maleki, S.J. et al. (2000) Structure of the major peanut allergen Ara h 1 may protect IgE-binding epitopes from degradation. J Immunol 164, 5844-5849CrossRefGoogle ScholarPubMed
34Suhr, M. et al. (2004) Isolation and characterization of natural Ara h 6: Evidence for a further peanut allergen with putative clinical relevance based on resistance to pepsin digestion and heat. Mol Nutr Food Res 48, 390-399CrossRefGoogle ScholarPubMed
35Lehmann, K. et al. (2006) Structure and stability of 2S albumin-type peanut allergens: implications for the severity of peanut allergic reactions. Biochem J 395, 463-472CrossRefGoogle ScholarPubMed
36Maleki, S.J. et al. (2003) The major peanut allergen, Ara h 2, functions as a trypsin inhibitor, and roasting enhances this function. J Allergy Clin Immunol 112, 190-195CrossRefGoogle ScholarPubMed
37Chung, S.Y. and Champagne, E.T. (1999) Allergenicity of Maillard reaction products from peanut proteins. J Agric Food Chem 47, 5227-5231CrossRefGoogle ScholarPubMed
38Maleki, S.J. et al. (2000) The effects of roasting on the allergenic properties of peanut proteins. J Allergy Clin Immunol 106, 763-768CrossRefGoogle ScholarPubMed
39Chung, S.Y. et al. (2002) High-oleic peanuts are not different from normal peanuts in allergenic properties. J Agric Food Chem 50, 878-882CrossRefGoogle Scholar
40Namiki, M. (1988) Chemistry of Maillard reactions: recent studies on the browning reaction mechanism and the development of antioxidants and mutagens. Adv Food Res 32, 115-184CrossRefGoogle ScholarPubMed
41Vila, L. et al. (2001) Role of conformational and linear epitopes in the achievement of tolerance in cow's milk allergy. Clin Exp Allergy 31, 1599-1606CrossRefGoogle ScholarPubMed
42Burks, A.W. et al. (1997) Mapping and mutational analysis of the IgE-binding epitopes on Ara h 1, a legume vicilin protein and a major allergen in peanut hypersensitivity. Eur J Biochem 245, 334-339CrossRefGoogle Scholar
43Stanley, J.S. et al. (1997) Identification and mutational analysis of the immunodominant IgE binding epitopes of the major peanut allergen Ara h 2. Arch Biochem Biophys 342, 244-253CrossRefGoogle ScholarPubMed
44Bannon, G.A. et al. (1999) Tertiary structure and biophysical properties of a major peanut allergen, implications for the production of a hypoallergenic protein. Int Arch Allergy Immunol 118, 315-316CrossRefGoogle Scholar
45Shin, D.S. et al. (1998) Biochemical and structural analysis of the IgE binding sites on Ara h1, an abundant and highly allergenic peanut protein. J Biol Chem 273, 13753-13759CrossRefGoogle ScholarPubMed
46Shreffler, W.G. et al. (2004) Microarray immunoassay: association of clinical history, in vitro IgE function, and heterogeneity of allergenic peanut epitopes. J Allergy Clin Immunol 113, 776-782CrossRefGoogle ScholarPubMed
47Glaspole, I.N. et al. (2005) Characterization of the T-cell epitopes of a major peanut allergen, Ara h 2. Allergy 60, 35-40CrossRefGoogle ScholarPubMed
48Ewan, P.W. (1996) Clinical study of peanut and nut allergy in 62 consecutive patients: new features and associations. BMJ 312, 1074-1078CrossRefGoogle ScholarPubMed
49Sicherer, S.H., Burks, A.W. and Sampson, H.A. (1998) Clinical features of acute allergic reactions to peanut and tree nuts in children. Pediatrics 102, e6CrossRefGoogle ScholarPubMed
50Parra, F.M. et al. (1993) Pistachio nut hypersensitivity: identification of pistachio nut allergens. Clin Exp Allergy 23, 996-1001CrossRefGoogle ScholarPubMed
51Sutherland, M.F. et al. (1999) Macadamia nut anaphylaxis: demonstration of specific IgE reactivity and partial cross-reactivity with hazelnut. J Allergy Clin Immunol 104, 889-890CrossRefGoogle ScholarPubMed
52de Leon, M.P. et al. (2003) Immunological analysis of allergenic cross-reactivity between peanut and tree nuts. Clin Exp Allergy 33, 1273-1280CrossRefGoogle ScholarPubMed
53de Leon, M.P. et al. (2007) IgE cross-reactivity between the major peanut allergen Ara h 2 and tree nut allergens. Mol Immunol 44, 463-471CrossRefGoogle ScholarPubMed
54Teuber, S.S. et al. (1999) Identification and cloning of a complementary DNA encoding a vicilin-like proprotein, Jug r 2, from English walnut kernel (Juglans regia), a major food allergen. J Allergy Clin Immunol 104, 1311-1320CrossRefGoogle Scholar
55Wang, F. et al. (2002) Ana o 1, a cashew (Anacardium occidental) allergen of the vicilin seed storage protein family. J Allergy Clin Immunol 110, 160-166CrossRefGoogle Scholar
56Pastorello, E.A. et al. (2002) Identification of hazelnut major allergens in sensitive patients with positive double-blind, placebo-controlled food challenge results. J Allergy Clin Immunol 109, 563-570CrossRefGoogle ScholarPubMed
57Poltronieri, P. et al. (2002) Identification and characterisation of the IgE-binding proteins 2S albumin and conglutin gamma in almond (Prunus dulcis) seeds. Int Arch Allergy Immunol 128, 97-104CrossRefGoogle ScholarPubMed
58Pastorello, E.A. et al. (1998) Sensitization to the major allergen of Brazil nut is correlated with the clinical expression of allergy. J Allergy Clin Immunol 102, 1021-1027CrossRefGoogle Scholar
59Teuber, S.S. et al. (1998) Cloning and sequencing of a gene encoding a 2S albumin seed storage protein precursor from English walnut (Juglans regia), a major food allergen. J Allergy Clin Immunol 101, 807-814CrossRefGoogle ScholarPubMed
60Wang, F. et al. (2003) Ana o 2, a major cashew (Anacardium occidentale L.) nut allergen of the legumin family. Int Arch Allergy Immunol 132, 27-39CrossRefGoogle Scholar
61Beyer, K. et al. (2002) Identification of an 11S globulin as a major hazelnut food allergen in hazelnut-induced systemic reactions. J Allergy Clin Immunol 110, 517-523CrossRefGoogle Scholar
62Teuber, S.S. et al. (2003) Identification and cloning of Jug r 4, a major food allergen from English walnut belonging to the legumin group. J Allergy Clin Immunol 111, S248CrossRefGoogle Scholar
63Bernhisel-Broadbent, J. and Sampson, H.A. (1989) Cross-allergenicity in the legume botanical family in children with food hypersensitivity. J Allergy Clin Immunol 83, 435-440CrossRefGoogle ScholarPubMed
64Bernhisel-Broadbent, J., Taylor, S. and Sampson, H.A. (1989) Cross-allergenicity in the legume botanical family in children with food hypersensitivity. II. Laboratory correlates. J Allergy Clin Immunol 84, 701-709CrossRefGoogle ScholarPubMed
65van der Veen, M.J. et al. (1997) Poor biologic activity of cross-reactive IgE directed to carbohydrate determinants of glycoproteins. J Allergy Clin Immunol 100, 327-334CrossRefGoogle ScholarPubMed
66Batanero, E. et al. (1996) Cross-reactivity between the major allergen from olive pollen and unrelated glycoproteins: evidence of an epitope in the glycan moiety of the allergen. J Allergy Clin Immunol 97, 1264-1271CrossRefGoogle ScholarPubMed
67Petersen, A. et al. (1996) Ubiquitous structures responsible for IgE cross-reactivity between tomato fruit and grass pollen allergens. J Allergy Clin Immunol 98, 805-815CrossRefGoogle ScholarPubMed
68de Leon, M.P. et al. (2005) Functional analysis of cross-reactive immunoglobulin E antibodies: peanut-specific immunoglobulin E sensitizes basophils to tree nut allergens. Clin Exp Allergy 35, 1056-1064CrossRefGoogle ScholarPubMed
69Burks, A.W., King, N. and Bannon, G.A. (1999) Modification of a major peanut allergen leads to loss of IgE binding. Int Arch Allergy Immunol 118, 313-314CrossRefGoogle Scholar
70King, N. et al. (2005) Allergenic characteristics of a modified peanut allergen. Mol Nutr Food Res 49, 963-971CrossRefGoogle ScholarPubMed
71Rabjohn, P. et al. (2002) Modification of peanut allergen Ara h 3: effects on IgE binding and T cell stimulation. Int Arch Allergy Immunol 128, 15-23CrossRefGoogle ScholarPubMed
72Bannon, G.A. et al. (2001) Engineering, characterization and in vitro efficacy of the major peanut allergens for use in immunotherapy. Int Arch Allergy Immunol 124, 70-72CrossRefGoogle ScholarPubMed
73Lewis, S.A. et al. (2005) The promiscuity of immunoglobulin E binding to peanut allergens, as determined by Western blotting, correlates with the severity of clinical symptoms. Clin Exp Allergy 35, 767-773CrossRefGoogle ScholarPubMed
74Briner, T. et al. (1993) Peripheral T cell tolerance induced in naive and primed mice by subcutaneous injection of peptides from the major cat allergen Fel d 1. Proc Natl Acad Sci USA 90, 7608-7612CrossRefGoogle Scholar
75Hoyne, G.F. et al. (1993) Inhibition of T cell and antibody responses to house dust mite allergen by inhalation of dominant T cell epitope in naive and sensitized mice. J Exp Med 178, 1783-1788CrossRefGoogle ScholarPubMed
76Oldfield, W.L., Larche, M. and Kay, A.B. (2002) Effect of T-cell peptides derived from Fel d 1 on allergic reactions and cytokine production in patients sensitive to cats: a randomised controlled trial. Lancet 360, 47-53CrossRefGoogle Scholar
77Alexander, C. et al. (2005) The effect of Fel d 1-derived T-cell peptides on upper and lower airway outcome measurements in cat-allergic subjects. Allergy 60, 1269-1274CrossRefGoogle Scholar
78Muller, U.R. et al. (1998) Successful immunotherapy with T cell epitope peptides of bee venom phospholipase A2 induces specific T cell anergy in bee sting allergic patients. J Allergy Clin Immunol 101, 747-757CrossRefGoogle Scholar
79Drew, A.C. et al. (2004) Hypoallergenic variants of the major latex allergen Hev b 6.01 retaining human T lymphocyte reactivity. J Immunol 173, 5872-5879CrossRefGoogle ScholarPubMed
80Leung, D.Y. et al. (2003) Effect of anti-IgE therapy in patients with peanut allergy. N Engl J Med 348, 986-993CrossRefGoogle ScholarPubMed
81Teuber, S.S. and Beyer, K. (2004) Peanut, tree nut and seed allergies. Curr Opin Allergy Clin Immunol 4, 201-203CrossRefGoogle ScholarPubMed
82Lee, S.Y. et al. (2001) Oral administration of IL-12 suppresses anaphylactic reactions in a murine model of peanut hypersensitivity. Clin Immunol 101, 220-228CrossRefGoogle Scholar
83Li, X.M. et al. (2001) Food Allergy Herbal Formula-1 (FAHF-1) blocks peanut-induced anaphylaxis in a murine model. J Allergy Clin Immunol 108, 639-646CrossRefGoogle ScholarPubMed
84Moingeon, P. et al. (2006) Immune mechanisms of allergen-specific sublingual immunotherapy. Allergy 61, 151-165CrossRefGoogle ScholarPubMed
85Dahl, R. et al. (2006) Efficacy and safety of sublingual immunotherapy with grass allergen tablets for seasonal allergic rhinoconjunctivitis. J Allergy Clin Immunol 118, 434-440CrossRefGoogle ScholarPubMed
86Bousquet, J. et al. (1999) Sublingual-swallow immunotherapy (SLIT) in patients with asthma due to house-dust mites: a double-blind, placebo-controlled study. Allergy 54, 249-260CrossRefGoogle ScholarPubMed
87Enrique, E. et al. (2005) Sublingual immunotherapy for hazelnut food allergy: a randomized, double-blind, placebo-controlled study with a standardized hazelnut extract. J Allergy Clin Immunol 116, 1073-1079CrossRefGoogle ScholarPubMed
88Aalberse, R.C. (2000) Structural biology of allergens. J Allergy Clin Immunol 106, 228-238CrossRefGoogle ScholarPubMed
89Aalberse, R.C., Akkerdaas, J.H. and van Ree, R. (2001) Cross-reactivity of IgE antibodies to allergens. Allergy 56, 478-490CrossRefGoogle ScholarPubMed
90Moseley, B.E. (2001) How to make foods safer–genetically modified foods. Allergy 56 Suppl 67, 61-63CrossRefGoogle ScholarPubMed
91Tada, Y. et al. (1996) Reduction of 14–16  kDa allergenic proteins in transgenic rice plants by antisense gene. FEBS Lett 391, 341-345CrossRefGoogle ScholarPubMed
92Herman, E.M. et al. (2003) Genetic modification removes an immunodominant allergen from soybean. Plant Physiol 132, 36-43CrossRefGoogle ScholarPubMed
93Dodo, H., Konan, K. and Viquez, O. (2005) A genetic engineering strategy to eliminate peanut allergy. Curr Allergy Asthma Rep 5, 67-73CrossRefGoogle ScholarPubMed
94Vaucheret, H., Beclin, C. and Fagard, M. (2001) Post-transcriptional gene silencing in plants. J Cell Sci 114, 3083-3091CrossRefGoogle ScholarPubMed
95Flicker, S. et al. (2006) Spatial clustering of the IgE epitopes on the major timothy grass pollen allergen Phl p 1: importance for allergenic activity. J Allergy Clin Immunol 117, 1336-1343CrossRefGoogle Scholar

Further reading, resources and contacts

The International Union of Immunological Societies Allergen (IUIS) Nomenclature Sub-committee website provides the official list of allergens:

http://www.allergen.org Google Scholar
http://www.allergome.orgGoogle Scholar