Authentication of food allergen quality by physicochemical and immunological methods

Clinical and Experimental Allergy

Volumn 40, Issue 7, 2010, Pages 973-986

  Sancho, A I ^a   Hoffmann Sommergruber, K ^b   Alessandri, S ^c   Conti, A ^d   Giuffrida, M G ^d   Shewry, P ^e   Jensen, B M ^f   Skov, P ^g   Vieths, S ^h  

^a INSTITUTE OF FOOD RESEARCH   (United Kingdom)

^b MEDICAL UNIVERSITY OF VIENNA   (Austria)

^c UNIVERSITY OF FLORENCE   (Italy)

^d INSTITUTE OF SCIENCES OF FOOD PRODUCTION   (Italy)

^e ROTHAMSTED RESEARCH   (United Kingdom)

^f Mental Health Services CPH   (Denmark)

^g Reference Laboratory   (Denmark)

^h PAUL EHRLICH INSTITUT   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

FOOD ALLERGEN; IMMUNOGLOBULIN E; RECOMBINANT ALLERGEN;

BIOLOGICAL ACTIVITY; CIRCULAR DICHROISM; DIAGNOSTIC TEST; FOOD ALLERGY; FOOD INDUSTRY; IMMUNOCHEMISTRY; IMMUNOTHERAPY; MASS SPECTROMETRY; NONHUMAN; NUCLEAR MAGNETIC RESONANCE; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN FOLDING; PROTEOMICS; PROVOCATION TEST; REVIEW; SEROLOGY;

ALLERGENS; CHEMISTRY, PHYSICAL; DESENSITIZATION, IMMUNOLOGIC; FOOD HYPERSENSITIVITY; HUMANS; IMMUNOHISTOCHEMISTRY; PROTEOMICS;

EID: 77953511310     PISSN: 09547894     EISSN: 13652222     Source Type: Journal    
DOI: 10.1111/j.1365-2222.2010.03534.x     Document Type: Review

References (111)

1. Bohle B, Vieths S. Improving diagnostic tests for food allergy with recombinant allergens. Methods 2004 32 : 292 299.
2. Lidholm J, Ballmer-Weber BK, Mari A, Vieths S. Component-resolved diagnostics in food allergy. Curr Opin Allergy Clin Immunol 2006 6 : 234 240.
3. Harwanegg C, Hiller R. Protein microarrays for the diagnosis of allergic diseases: state-of-the-art and future development. Clin Chem Lab Med 2005 43 : 1321 1326.
4. Dufva M, Christensen CBV. Diagnostic and analytical applications of protein microarrays. Expert Rev Proteomics 2005 2 : 41 8.
5. Ferreira F, Wallner M, Breiteneder H, Hartl A, Thalhamer J, Ebner C. Genetic engineering of allergens: Future therapeutic products. Int Arch Allergy Immunol 2002 128 : 171 178.
6. Cromwell O, Fiebig H, Suck R et al. Strategies for recombinant allergen vaccines and fruitful results from first clinical studies. Immunol Allergy Clin North America 2006 26 : 261 281.
7. Lorenz AR, Luttkopf D, Seitz R, Vieths S. The Regulatory system in Europe with special emphasis on Allergen products. Int Arch Allergy Immunol 2008 147 : 263 275.
8. Specifications. Test procedures and acceptance criteria for biotechnological/biological products (ICH Q6B;CPMP/ICH/365/96). EMEA, Human Medicines Evaluation Unit, 1996.
9. Draft guideline on allergen products. Production and quality issues. EMEA/CHMP/BWP/304831/2007. Committee for Medicinal Products for Human Use (CHMP), 2007.
10. Hoffmann-Sommergruber K, Mills ENC, Vieths S. Coordinated and standardized production, purification and characterization of natural and recombinant food allergens to establish a food allergen library. Mol Nutr Food Res 2008 52 : S159 65.
11. Vieths S, Hoffmann-Sommergruber K. EuroPrevall food allergen library. Mol Nutr Food Res 2008 52 : S157 58.
12. Bauermeister K, Ballmer-Weber BK, Bublin M et al. Assessment of component-resolved in vitro diagnosis of celeriac allergy. J Allergy Clin Immunol 2009 124 : 1273 1281.
13. Bublin M, Pfister M, Radauer C et al. Component-resolved diagnosis of kiwifruit allergy with purified natural and recombinant kiwifruit allergens. J Allergy Clin Immunol 2010 125 : 687 694.
14. Ballmer-Weber BK, Scheurer S, Fritsche P et al. Component-resolved diagnosis with recombinant allergens in patients with cherry allergy. J Allergy Clin Immunol 2002 110 : 167 173.
15. Schocker F, Luttkopf D, Scheurer S et al. Recombinant lipid transfer protein Cor a 8 from hazelnut: A new tool for in vitro diagnosis of potentially severe hazelnut allergy. J Allergy Clin Immunol 2004 113 : 141 147.
16. Fernandez-Rivas M, Bolhaar S, Gonzalez-Mancebo E et al. Apple allergy across Europe: How allergen sensitization profiles determine the clinical expression of allergies to plant foods. J Allergy Clin Immunol 2006 118 : 481 488.
17. Gaier S, Oberhuber C, Hemmer W et al. Pru p 3 as a marker for symptom severity for patients with peach allergy in a birch pollen environment. J Allergy Clin Immunol 2009 124 : 166 167.
18. Asero R, Mistrello G, Roncarolo D et al. Detection of clinical markers of sensitization to profilin in patients allergic to plant-derived foods. J Allergy Clin Immunol 2003 112 : 427 432.
19. Lopez-Torrejon G, Crespo JF, Sanchez-Monge R et al. Allergenic reactivity of the melon profilin Cuc m 2 and its identification as major allergen. Clin Exp Allergy 2005 35 : 1065 1072. (Pubitemid 41603141)
20. Crespo JF, Retzek M, Foetisch K et al. Germin-like protein Cit s 1 and profilin Cit s 2 are major allergens in orange (Citrus sinensis) fruits. Mol Nutr Food Res 2006 50 : 282 290.
21. Ballmer-Weber BK, Vieths S, Luttkopf D, Heuschmann P, Wuthrich B. Celery allergy confirmed by double-blind, placebo-controlled food challenge: a clinical study in 32 subjects with a history of adverse reactions to celery root. J Allergy Clin Immunol 2000 106 : 373 378.
22. Ballmer-Weber BK, Holzhauser T, Scibilia J et al. Clinical characteristics of soybean allergy in Europe: A double-blind, placebo-controlled food challenge study. J Allergy Clin Immunol 2007 119 : 1489 1496.
23. Himly M, Nony E, Chabre H et al. Standardization of allergen products: 1. detailed characterization of GMP-produced recombinant Bet v 1.0101 as biological reference preparation. Allergy 2009 64 : 1038 1045.
24. Wallner M, Gruber P, Radauer C et al. Lab scale and medium scale production of recombinant allergens in Escherichia coli. Methods 2004 32 : 219 226.
25. Marsh J, Rigby N, Wellner K et al. Purification and characterisation of a panel of peanut allergens suitable for use in allergy diagnosis. Mol Nutr Food Res 2008 52 : S272 85.
26. Rigby NM, Marsh J, Sancho AI et al. The purification and characterisation of allergenic hazelnut seed proteins. Mol Nutr Food Res 2008 52 : S251 61.
27. Blanc F, Bernard H, Alessandri S et al. Update on optimized purification and characterization of natural milk allergens. Mol Nutr Food Res 2008 52 : S166 75.
28. Hoffmann-Sommergruber K, Ferris R, Pec M et al. Characterization of Api g 1.0201, a new member of the Api g 1 family of celery allergens. Int Arch Allergy Immunol 2000 122 : 115 123.
29. Lauer I, Alessandri S, Pokoj S et al. Expression and characterization of three important panallergens from hazelnut. Mol Nutr Food Res 2008 52 : S262 71.
30. Pons L, Chery C, Romano A, Namour F, Artesani MC, Gueant JL. The 18 kDa peanut oleosin is a candidate allergen for IgE-mediated reactions to peanuts. Allergy 2002 57 : 88 93.
31. Zaborsky N, Brunner M, Wallner M et al. Antigen Aggregation decides the fate of the allergic immune response. J Immunol 2010 184 : 725 735.
32. Gao ZS, van de Weg WE, Schaart JG et al. Linkage map positions and allelic diversity of two Mal d 3 (non-specific lipid transfer protein) genes in the cultivated apple (Malus domestica). Theor Appl Genetics 2005 110 : 479 491.
33. Ma Y, Zuidmeer L, Bohle B et al. Characterization of recombinant Mal d 4 and its application for component-resolved diagnosis of apple allergy. Clin Exp Allergy 2006 36 : 1087 1096.
34. Dobson C. Protein folding and misfolding. Nature 2003 426 : 884 890.
35. Dewan JC, Mikami B, Hirose M, Sacchettini JC. Structural Evidence for A Ph-Sensitive Dilysine Trigger in the Hen Ovotransferrin N-Lobe - Implications for Transferrin Iron Release. Biochemistry 1993 32 : 11963 11968.
36. Tatham AS, Wellner N. Spectroscopic analysis of gluten structure:circular dichroism and infra-red. In : Shewry P, Lookhart GL, eds. Wheat gluten protein analysis.
37. Gaier S, Marsh J, Oberhuber C et al. Purification and structural stability of the peach allergens Pru p 1 and Pru p 3. Mol Nutr Food Res 2008 52 : S220 29.
38. Mueller S, Wieser H. The location of disulphide bonds in monomeric gamma-type gliadins. J Cereal Sci 1997 26 : 169 176.
39. Fukuyama Y, Iwamoto S, Tanaka K. Rapid sequencing and disulfide mapping of peptides containing disulfide bonds by using 1,5-diaminoanaphthalene as a reductive matrix. J Mass Spect 2006 41 : 191 201.
40. Reese G, Ballmer-Weber BK, Wangorsch A, Randow S, Vieths S. Allergenicity and antigenicity of wild-type and mutant, monomeric, and dimeric carrot major allergen Dau c: Destruction of conformation, not oligomerization, is the roadmap to save allergen vaccines. J Allergy Clin Immunol 2007 119 : 944 951.
41. Ferreira F, Hirtenlehner K, Jilek A et al. Dissection of immunoglobulin E and T lymphocyte reactivity of isoforms of the major birch pollen allergen Bet v: Potential use of hypoallergenic isoforms for immunotherapy. J Exp Med 1996 183 : 599 609.
42. Wagner S, Radauer C, Bublin M et al. Naturally occurring hypoallergenic Bet v 1 isoforms fail to induce IgE responses in individuals with birch pollen allergy. J Allergy Clin Immunol 2008 121 : 246 252.
43. Vrtala S, Hirtenlehner K, Susani M et al. Genetic engineering of a hypoallergenic trimer of the major birch pollen allergen, Bet v 1. FASEB J 2001 15 : 2045 2047.
44. van Ree R, Chapman MD, Ferreira F et al. The CREATE Project: development of certified reference materials for allergenic products and validation of methods for their quantification. Allergy 2008 63 : 310 326.
45. Albrecht M, Alessandri S, Conti A et al. High level expression, purification and physico- and immunochemical characterisation of recombinant Pen a 1: A major allergen of shrimp. Mol Nutr Food Res 2008 52 : S186 95.
46. Oberhuber C, Ma Y, Marsh J et al. Purification and characterisation of relevant natural and recombinant apple allergens. Mol Nutr Food Res 2008 52 : S208 19.
47. Bublin M, Lauer I, Oberhuber C et al. Production and characterization of an allergen panel for component-resolved diagnosis of celery allergy. Mol Nutr Food Res 2008 52 : S241 50.
48. Ma Y, Griesmeier U, Susani M et al. Comparison of natural and recombinant forms of the major fish allergen parvalbumin from cod and carp. Mol Nutr Food Res 2008 52 : S196 207.
49. Jacobsen B, Hoffmann-Sommergruber K, Have TT et al. The panel of egg allergens, Gal d 1-Gal d 5: their improved purification and characterization. Mol Nutr Food Res 2008 52 : S176 85.
50. Svergun DI, Koch MHJ. Advances in structure analysis using small-angle scattering in solution. Curr Opin Struct Biol 2002 12 : 654 660.
51. Bublin M, Radauer C, Wilson IBH et al. Cross-reactive N-glycans of Api g 5, a high molecular weight glycoprotein allergen from celery, are required for immunoglobulin E binding and activation of effector cells from allergic patients. FASEB J 2003 17 : 1697 1699.
52. Prescott VE, Campbell PM, Moore A et al. Transgenic expression of bean alpha-amylase inhibitor in peas results in altered structure and immunogenicity. J Agri Food Chem 2005 53 : 9023 9030.
53. Butters TD. Glycoprotein analysis. In : Rapley R, Walker JM, eds. Molecular Biomethods Handbook.
54. Mirgorodskaya E, Krogh TN, Roepstorff P. Characterization of protein glycosylation by MALDI-TOFMS. In : Chapman JR, ed. Mass Spectrometry of Proteins and Peptides. Methods in Molecular Biology.
55. Stephens E, Maslen SL, Green LG, Williams DH. Fragmentation characteristics of neutral N-linked glycans using a MALDI-TOF/TOF tandem mass spectrometer. Analyt Chem 2004 76 : 2343 2354.
56. Jenkins JA, Breiteneder H, Mills ENC. Evolutionary distance from human homologs reflects allergenicity of animal food proteins. J Allergy Clin Immunol 2007 120 : 1399 1405.
57. Radauer C, Bublin M, Wagner S, Mari A, Breiteneder H. Allergens are distributed into few protein families and possess a restricted number of biochemical functions. J Allergy Clin Immunol 2008 121 : 847 852.
58. Wiley PR, Tosi P, Evrard A, Lovegrove A, Jones HD, Shewry PR. Promoter analysis and immunolocalisation show that puroindoline genes are exclusively expressed in starchy endosperm cells of wheat grain. Plant Mol Biol 2007 64 : 125 136.
59. Brett GM, Mills ENC, Goodfellow BJ et al. Epitope mapping studies of broad specificity monoclonal antibodies to cereal prolamins. J Cereal Sci 1999 29 : 117 128.
60. Mills ENC, Field JM, Kauffman JA, Tatham AS, Shewry PR, Morgan MRA. Characterization of a monoclonal antibody specific for HMW subunits of glutenin and its use to investigate glutenin polymers. J Agri Food Chem 2000 48 : 611 617.
61. Lamberti C, Pessione E, Giuffrida MG et al. Combined cup loading, bis(2-hydroxyethyl) disulfide, and protein precipitation protocols to improve the alkaline proteome of Lactobacillus hilgardii. Electrophoresis 2007 28 : 1633 1638.
62. Herbert B, Galvani M, Hamdan M et al. Reduction and alkylation of proteins in preparation of two-dimensional map analysi: Why, when, and how? Electrophoresis 2001 22 : 2046 2057.
63. Ballmer-Weber BK, Wangorsch A, Bohle B et al. Component-resolved in vitro diagnosis in carrot allergy: Does the use of recombinant carrot allergens improve the reliability of the diagnostic procedure? Clin Exp Allergy 2005 35 : 970 978.
64. Ros A, Faupel M, Mees H et al. Protein purification by Off-Gel electrophoresis. Proteomics 2002 2 : 151 156.
65. ® Ruby Dyes. In : Walker JM, ed. The proteomics protocols handbook.
66. Reuter A, Fortunato D, Garoffo LP et al. Novel isoforms of Pru av 1 with diverging immunoglobulin E binding properties identified by a synergistic combination of molecular biology and proteomics. Proteomics 2005 5 : 282 289.
67. Herndl A, Marzban G, Kolarich D et al. Mapping of Malus domestica allergens by 2-D electrophoresis and IgE-reactivity. Electrophoresis 2007 28 : 437 448.
68. Gonzalez-Buitrago JM, Ferreira L, Isidoro-Garcia M, Sanz C, Lorente F, Davila I. Proteomic approaches for identifying new allergens and diagnosing allergic diseases. Clin Chim Acta 2007 385 : 21 7.
69. Yanagida M. Functional proteomics; current achievements. J Chromatogr B Analyt Technol Biomed Life Sci 2002 771 : 89 106.
70. Pappin DJC, Hojrup P, Bleasby AJ. Rapid identification of proteins by peptide-mass fingerprinting. Curr Biol 1993 3 : 327 332.
71. Helsper JPFG, Gilissen LJWJ, van Ree R, America AHP, Cordewener JHG, Bosch D. Quadrupole time-of-flight mass spectrometry: a method to study the actual expression of allergen isoforms identified by PCR cloning. J Allergy Clin Immunol 2002 110 : 131 138.
72. Moreno FJ, Jenkins JA, Mellon FA et al. Mass spectrometry and structural characterization of 2S albumin isoforms from Brazil nuts (Bertholletia excelsa). Biochim Biophys Acta 2004 1698 : 175 186.
73. Ayuso R, Grishina G, Bardina L et al. Myosin light chain is a novel shrimp allergen, Lit v 3. J Allergy Clin Immunol 2008 122 : 795 802.
74. Hewick RM, Hunkapiller MW, Hood LE, Dreyer WJ. A Gas-Liquid Solid-Phase Peptide and Protein Sequenator. J Biol Chem 1981 256 : 7990 7997.
75. Oberhuber C, Bulley SM, Ballmer-Weber BK et al. Characterization of Bet v 1-related allergens from kiwifruit relevant for patients with combined kiwifruit and birch pollen allergy. Mol Nutr Food Res 2008 52 : S230 40.
76. Kelly SM, Jess TJ, Price NC. How to study proteins by circular dichroism. Biochim Biophys Acta 2005 1751 : 119 139.
77. Verdino P, Keller W. Circular dichroism analysis of allergens. Methods 2004 32 : 241 248.
78. Kelly SM, Price NC. The use of circular dichroism in the investigation of protein structure and function. Curr Protein Pept Sci 2000 1 : 349 384.
79. Swoboda I, Bugajska-Schretter A, Linhart B et al. A recombinant hypoallergenic parvalbumin mutant for immunotherapy of IgE-mediated fish allergy. J Immunol 2007 178 : 6290 6296.
80. Moreno FJ, Mackie AR, Mills ENC. Phospholipid interactions protect the milk allergen alpha-lactalbumin from proteolysis during in vitro digestion. J Agr Food Chem 2005 53 : 9810 9816.
81. Sancho AI, Rigby NM, Zuidmeer L et al. The effect of thermal processing on the IgE reactivity of the non-specific lipid transfer protein from apple, Mal d 3. Allergy 2005 60 : 1262 1268.
82. Sen M, Kopper R, Pons L, Abraham EC, Burks AW, Bannon GA. Protein structure plays a critical role in peanut allergen stability and may determine immunodominant IgE-binding epitopes. J Immunol 2002 169 : 882 887.
83. Rehm T, Huber R, Holak TA. Application of NMR in structural proteomics: screening for proteins amenable to structural analysis. Structure 2002 10 : 1613 1618.
84. Berman HM, Westbrook J, Feng Z et al. The Protein Data Bank. Nucleic Acids Res 2000 28 : 235 242.
85. Kurokawa H, Mikami B, Hirose M. Crystal-structure of Diferric Hen Ovotransferrin at 2.4 Angstrom resolution. J Mol Biol 1995 254 : 196 207.
86. Asero R, Ballmer-Weber BK, Beyer K et al. IgE-mediated food allergy diagnosis: current status and new perspectives. Mol Nutr Food Res 2007 51 : 135 147.
87. Lombardero M, Heymann PW, Plattsmills TAE, Fox JW, Chapman MD. Conformational Stability of B-cell epitopes on Group-I and Group-Ii Dermatophagoides Spp Allergens - Effect of thermal and chemical denaturation on the binding of murine IgG and human IgE antibodies. J Immunol 1990 144 : 1353 1360.
88. Wensing M, Akkerdaas JH, van Leeuwen A et al. IgE to Bet v 1 and profilin: cross-reactivity patterns and clinical relevance. J Allergy Clin Immunol 2002 110 : 435 442.
89. Osterballe M, Hansen TK, Mortz CG, Bindslev-Jensen C. The clinical relevance of sensitization to pollen-related fruits and vegetables in unselected pollen-sensitized adults. Allergy 2005 60 : 218 225.
90. Mari A, Iacovacci P, Afferni C et al. Specific IgE to cross-reactive carbohydrate determinants strongly affect the in vitro diagnosis of allergic diseases. J Allergy Clin Immunol 1999 103 : 1005 1011.
91. Bolhaar STHP, Zuidmeer L, Ma Y et al. A mutant of the major apple allergen, Mal d 1, demonstrating hypo-allergenicity in the target organ by double-blind placebo-controlled food challenge. Clin Exp Allergy 2005 35 : 1638 1644.
92. Flinterman AE, van Hoffen E, Jager CFD et al. Children with peanut allergy recognize predominantly Ara h2 and Ara h6, which remains stable over time. Clin Exp Allergy 2007 37 : 1221 1228.
93. Asero R, Jimeno L, Barber D. Component-resolved diagnosis of plant food allergy by SPT. Eur Ann Allergy Clin Immunol 2008 40 : 115 121.
94. Chirumbolo S, Vella A, Ortolani R et al. Differential response of human basophil activation markers: a multi-parameter flow cytometry approach. Clin Mol Allergy 2008 16 : 6 12.
95. Ocmant A, Mullier S, Hanssens L et al. Basophil activation tests for the diagnosis of food allergy in children. Clin Exp Allergy 2009 39 : 1234 1245.
96. Wallowitz ML, Chen RJ, Tzen JT, Teuber SS. Ses i 6, the sesame 11S globulin, can activate basophils and shows cross-reactivity with walnut in vitro. Clin Exp Allergy 2007 37 : 929 938.
97. Erdmann SM, Sachs B, Schmidt A et al. In vitro analysis of birch-pollen-associated food allergy by use of recombinant allergens in the basophil activation test. Int Arch Allergy Immunol 2005 136 : 230 238.
98. Skov PS, Mosbech H, Norn S WB. Sensitive glass microfibre-based histamine analysis for allergy testing in washed blood cells. Results compared with conventional leukocyte histamine release assay. Allergy 1985 40 : 213 218.
99. Sturm GJ, Kranzelbinder B, Sturm EM, Heinemann A, Groselj-Strele A, Aberer W. The basophil activation test in the diagnosis of allergy: technical issues and critical factors. Allergy 2009 64 : 1319 1326.
100. Sanz ML, Sanchez G, Gamboa PM et al. Allergen-induced basophil activation: CD63 cell expression detected by flow cytometry in patients allergic to Dermatophagoides pteronyssinus and Lolium perenne. Clin Exp Allergy 2001 31 : 1007 1013.
101. Hansen KS, Ballmer-Weber BK, Luttkopf D et al. Roasted hazelnuts - allergenic activity evaluated by double-blind, placebo-controlled food challenge. Allergy 2003 58 : 132 138.
102. Luttkopf D, Muller U, Skov PS et al. Comparison of four variants of a major allergen in hazelnut (Corylus avellana) Cor a 1.04 with the major hazel pollen allergen Cor a 1.01. Mol Immunol 2001 38 : 515 525.
103. Budde IK, de Heer PG, Natter S et al. Studies on the association between immunoglobulin E autoreactivity and immunoglobulin E-dependent histamine-releasing factors. Immunology 2002 107 : 243 251.
104. Nolte H, Poulsen LK, Schiotz PO, Skov PS. Passive sensitization and histamine release of basophils. IgE and cellular factors regulating histamine release. Allergy 1990 45 : 427 435.
105. Pedersen MH, Holzhauser T, Bisson C et al. Soybean allergen detection methods - a comparison study. Mol Nutr Food Res 2008 52 : 1486 1496.
106. Poulsen LK, Pedersen MH, Platzer M et al. Immunochemical and biological quantification of peanut extract. Arb Paul Ehrlich Inst Bundesamt Sera Impfstoffe Frankf A M 2003 94 : 97 105.
107. Bohle B. T lymphocytes and food allergy. Mol Nutr Food Res 2004 48 : 424 433.
108. Bohle B. The impact of pollen-related food allergens on pollen allergy. Allergy 2007 62 : 3 10. (Pubitemid 44902728)
109. Bannon GA, Cockrell G, Connaughton C et al. Engineering, characterization and in vitro efficacy of the major peanut allergens for use in immunotherapy. Int Arch Allergy Immunol 2001 124 : 70 2.
110. Rabjohn P, West CM, Connaughton C et al. Modification of peanut allergen Ara h 3: effects on IgE binding and T cell stimulation. Int Arch Allergy Immunol 2002 128 : 15 23.
111. Ma Y, Gadermaier G, Bohle B et al. Mutational analysis of amino acid positions crucial for IgE-binding epitopes of the major apple (Malus domestica) allergen, Mal d 1. Int Arch Allergy Immunol 2006 139 : 53 62.