Home Medicine Allergy testing: the role of recombinant allergens
Article
Licensed
Unlicensed Requires Authentication

Allergy testing: the role of recombinant allergens

  • Nadine Mothes , Rudolf Valenta and Susanne Spitzauer
Published/Copyright: February 13, 2006

Abstract

Currently, diagnosis of type I allergy is performed using crude allergen extracts, which allow the identification of the allergen-containing source responsible for type I allergic symptoms (e.g., allergic rhino-conjunctivitis, asthma) but not the disease-eliciting molecules. With the introduction of recombinant allergens produced by molecular biology techniques, a large panel of allergenic molecules has become available. The application of these recombinant allergens for in vitro tests has led to new forms of component-resolved diagnosis (CRD) and allows the establishment of a patient's individual reactivity profile. The increasing number of recombinant allergens characterized during the last decade has allowed the development of chip-based allergy tests for simultaneous detection of up to 5000 different allergens and epitopes. The introduction of these recombinant allergen-based tests into clinical practice improves the selection of patients for traditional specific immunotherapy and allows monitoring of the immunological efficacy of specific immunotherapy by measuring allergen-specific IgG antibodies. Besides their diagnostic application, recombinant allergens and hypoallergenic derivatives thereof have also been used as vaccines in clinical trials, and recent results have shown their usefulness for the treatment of type I allergy.


Corresponding author: Prof. Dr. Susanne Spitzauer, Institut für Medizinische und Chemische Labordiagnostik, AKH, Medizinische Universität Wien, Währinger Gürtel 18-20, 1090 Vienna, Austria Phone: +43-1-40400-5324, Fax: +43-1-40400-5389,

References

1. Casolaro S, Georas SN, Song Z, Ono SJ. Biology and genetics of atopic disease. Curr Opin Immunol 1996; 8:796–803.10.1016/S0952-7915(96)80007-0Search in Google Scholar

2. Kay AB. Allergy and allergic diseases. Oxford: Blackwell Science, 1997.Search in Google Scholar

3. Wills-Karp M, Santeliz J, Karp CL. The germless theory of allergic disease: revisiting the hygiene hypothesis. Nat Rev Immunol 2001; 1:69–75.10.1038/35095579Search in Google Scholar

4. Segal DM, Taurog JD, Metzger H. Dimeric immunoglobulin E serves as a unit signal for mast cell degranulation. Proc Natl Acad Sci USA 1977; 74:2993–7.10.1073/pnas.74.7.2993Search in Google Scholar

5. van der Veen MJ, Mulder M, Witteman AM, van Ree R, Aalberse RC, Jansen HM, et al. False-positive skin prick test responses to commercially available dog dander extracts caused by contamination with house dust mite (Dermatophagoides pteronyssinus) allergens. J Allergy Clin Immunol 1996; 98:1028–32.10.1016/S0091-6749(96)80187-4Search in Google Scholar

6. Valenta R, Kraft D. Recombinant allergens for diagnosis and therapy of allergic diseases. Curr Opin Immunol 1995; 7:751–6.10.1016/0952-7915(95)80043-3Search in Google Scholar

7. Valenta R, Duchene M, Vrtala S, Birkner T, Ebner C, Hirschwehr R, et al. Recombinant allergens for immunoblot diagnosis of tree-pollen allergy. J Allergy Clin Immunol 1991; 88:889–94.10.1016/0091-6749(91)90245-JSearch in Google Scholar

8. Valenta R, Vrtala S, Ebner C, Kraft D, Scheiner O. Diagnosis of grass pollen allergy with recombinant timothy grass (Phleum pratense) pollen allergens. Int Arch Allergy Immunol 1992; 97:287–94.10.1159/000236135Search in Google Scholar

9. Ebner C, Szepfalusi Z, Ferreira F, Jilek A, Valenta R, Parronchi P, et al. Identification of multiple T cell epitopes on Bet v 1; the major birch pollen allergen, using specific T cell clones and overlapping peptides. J Immunol 1993; 150:1047–54.10.4049/jimmunol.150.3.1047Search in Google Scholar

10. Valenta R, Sperr WR, Ferreira F, Valent P, Sillaber C, Tejkl M, et al. Induction of specific histamine release from basophils with purified natural and recombinant birch pollen allergens. J Allergy Clin Immunol 1993; 91:88–97.10.1016/0091-6749(93)90300-5Search in Google Scholar

11. Sehon AH, Mohapatra SS. Induction of IgE antibodies in mice with recombinant grass pollen allergens. J Allergy Clin Immunol 1993; 91:88–97.Search in Google Scholar

12. Ferreira F, Mayer P, Sperr WR, Valent P, Seiberler S, Ebner C, et al. Induction of IgE antibodies with predefined specificity in rhesus monkeys with recombinant birch pollen allergens, Bet v 1 and Bet v 2. J Allergy Clin Immunol 1996; 97:95–103.10.1016/S0091-6749(96)70287-7Search in Google Scholar

13. Vrtala S, Mayer P, Ferreira F, Susani M, Sehon AH, Kraft, et al. Induction of IgE antibodies in mice and rhesus monkeys with recombinant birch pollen allergens: different allergenicity of Bet v 1 and Bet v 2. J Allergy Clin Immunol 1996; 98:913–21.10.1016/S0091-6749(96)80007-8Search in Google Scholar

14. Moser M, Crameri R, Brust E, Suter M, Mentz G. Diagnostic value of recombinant Aspergillus fumigatus allergen I/a for skin testing and serology. J Allergy Clin Immunol 1994; 93:1–11.10.1016/0091-6749(94)90227-5Search in Google Scholar

15. Müller UR, Dudler T, Schneider T, Crameri R, Fischer H, Skrbic D, et al. Type I skin reactivity to native and recombinant phospholipase A2 from honeybee venom is similar. J Allergy Clin Immunol 1995; 96:395–402.10.1016/S0091-6749(95)70059-5Search in Google Scholar

16. Menz G, Dolecek C, Schönheit-Kenn U, Ferreira F, Moser M, Schneider T, et al. Serological and skin-test diagnosis of birch pollen allergy with recombinant Bet v 1, the major birch pollen allergen. Clin Exp Allergy 1996; 26:50–60.10.1111/j.1365-2222.1996.tb00056.xSearch in Google Scholar

17. Pauli G, Oster JP, Deviller P, Heiss S, Bessot JC, Susani M, et al. Skin testing with recombinant allergens rBet v 1 and birch profilin, rBet v 2: diagnostic value for birch pollen and associated allergies. J Allergy Clin Immunol 1996; 97:1100–9.10.1016/S0091-6749(96)70264-6Search in Google Scholar

18. Lynch NR, Thomas WR, Chua Y, Garcia N, Diprisco MC, Lopez R. In vivo biological activity of recombinant Der p 2 allergen of house-dust mite. Int Arch Allergy Immunol 1994; 105:70–4.10.1159/000236805Search in Google Scholar

19. Sidoli A, Tamborini E, Giuntini I, Levi S, Volonte G, Paini C, et al. Cloning, expression and immunological characterization of recombinant Lolium perenne allergen Lol p II. J Biol Chem 1993; 268:21819–25.10.1016/S0021-9258(20)80615-2Search in Google Scholar

20. Valenta R, Lidholm J, Niederberger V, Hayek B, Kraft D, Grönlund H. The recombinant allergen-based concept of component-resolved diagnostics and immunotherapy (CRD and CRIT). Clin Exp Allergy 1999; 29:896–904.10.1046/j.1365-2222.1999.00653.xSearch in Google Scholar PubMed

21. Hiller R, Laffer S, Harwanegg C, Huber M, Schmidt WM, Twardosz A, et al. Microarrayed allergen molecules: diagnostic gatekeepers for allergy treatment. FASEB J 2002; 16:414–6.10.1096/fj.01-0711fjeSearch in Google Scholar PubMed

22. Harwanegg C, Laffer S, Hiller R, Mueller MW, Kraft D, Spitzauer S, et al. Microarrayed recombinant allergens for diagnosis of allergy. Clin Exp Allergy 2003; 33:7–13.10.1046/j.1365-2222.2003.01550.xSearch in Google Scholar PubMed

23. Suck R, Nandy A, Weber B, Stock M, Fiebig H, Cromwell O. Rapid method for arrayed investigation of IgE-reactivity profiles using natural and recombinant allergens. Allergy 2002; 57:821–4.10.1034/j.1398-9995.2002.23705.xSearch in Google Scholar PubMed

24. Deinhofer K, Sevcik H, Balic N, Harwanegg C, Hiller R, Rumpold H, et al. Microarrayed allergens for IgE profiling. Methods 2004; 32:249–54.10.1016/j.ymeth.2003.08.018Search in Google Scholar

25. Ball T, Sperr WR, Valent P, Lidholm J, Spitzauer S, Ebner C, et al. Induction of antibody responses to new B cell epitopes indicates vaccination character of allergen immunotherapy. Eur J Immunol 1999; 29:2026–36.10.1002/(SICI)1521-4141(199906)29:06<2026::AID-IMMU2026>3.0.CO;2-2Search in Google Scholar

26. Mothes N, Heinzkill M, Drachenberg KJ, Sperr WR, Krauth MT, Majlesi Y, et al. Allergen-specific immunotherapy with a monophosphoryl lipid A-adjuvanted vaccine: reduced seasonally boosted immunoglobulin E production and inhibition of basophil histamine release by therapy-induced blocking antibodies. Clin Exp Allergy 2003; 33:1198–208.10.1046/j.1365-2222.2003.01699.xSearch in Google Scholar

27. van Neerven RJ, Wikborg T, Lund G, Jacobsen B, Brinch-Nielsen A, Arnved J, et al. Blocking antibodies induced by specific allergy vaccination prevent the activation of CD4+ T cells by inhibiting serum-IgE-facilitated allergen presentation. J Immunol 1999; 163:2944–52.10.4049/jimmunol.163.5.2944Search in Google Scholar

28. Flicker S, Valenta R. Renaissance of the blocking antibody concept in type I allergy. Int Arch Allergy Immunol 2003; 132:13–24.10.1159/000073260Search in Google Scholar

29. Nouri-Aria KT, Wachholz PA, Francis JN, Jacobson MR, Walker SM, Wilcock LK, et al. Grass pollen immunotherapy induces mucosal and peripheral IL-10 responses and blocking IgG activity. J Immunol 2004; 172:3252–9.10.4049/jimmunol.172.5.3252Search in Google Scholar

30. Wachholz PA, Soni NK, Till SJ, Durham SR. Inhibition of allergen-IgE binding to B cells by IgG antibodies after grass pollen immunotherapy. J Allergy Clin Immunol 2003; 112:915–22.10.1016/S0091-6749(03)02022-0Search in Google Scholar

31. Wachholz PA, Durham SR. Mechanisms of immunotherapy: IgG revisited. Curr Opin Allergy Clin Immunol 2004; 4:313–8.10.1097/01.all.0000136753.35948.c0Search in Google Scholar

32. Niederberger V, Horak F, Vrtala S, Spitzauer S, Krauth MT, Valent P, et al. Vaccination with genetically engineered allergens prevents progression of allergic disease. Proc Natl Acad Sci USA 2004; 101:14677–82.10.1073/pnas.0404735101Search in Google Scholar

33. Reisinger J, Horak F, Pauli G, van Hage-Hamsten M, Cromwell O, König F, et al. Allergen-specific nasal IgG antibodies induced by vaccination with genetically modified allergens are associated with reduced nasal allergen sensitivity. J Allergy Clin Immunol 2005; 116:347–54.10.1016/j.jaci.2005.04.003Search in Google Scholar

34. Marsh DG, Goodfriend L, King TP, Lowenstein H, Platts-Mills TA. Allergen nomenclature. Bull World Health Organ 1986; 64:767–74.Search in Google Scholar

35. Pauli G. Evolution in the understanding of cross-reactivities of respiratory allergens: the role of recombinant allergens. Int Arch Allergy Immunol 2000; 123:183–95.10.1159/000024443Search in Google Scholar

36. Valenta R, Duchene M, Ebner C, Valent P, Sillaber C, Deviller P, et al. Profilins constitute a novel family of functional plant pan-allergens. J Exp Med 1992; 175:377–85.10.1084/jem.175.2.377Search in Google Scholar PubMed PubMed Central

37. Vallier P, DeChamp C, Valenta R, Vial O, Deviller P. Purification and characterization of an allergen from celery immunochemically related to an allergen present in several other plant species. Identification as a profilin. Clin Exp Allergy 1992; 22:774–82.10.1111/j.1365-2222.1992.tb02818.xSearch in Google Scholar PubMed

38. van Ree R, Voitenko V, van Leeuwen WA, Aalberse RC. Profilin is a cross-reactive allergen in pollen and vegetable foods. Int Arch Allergy Immunol 1992; 98:97–104.10.1159/000236171Search in Google Scholar PubMed

39. Moverare R, Westritschnig K, Svensson M, Hayek B, Bende M, Pauli G, et al. Different IgE reactivity profiles in birch pollen-sensitive patients from six European populations revealed by recombinant allergens: an imprint of local sensitization. Int Arch Allergy Immunol 2002; 128:325–35.10.1159/000063855Search in Google Scholar PubMed

40. Moverare R, Elfman L, Vesterinen E, Metso T, Haahtela T. Development of new IgE specificities to allergenic components in birch pollen extract during specific immunotherapy studied with immunoblotting and the Pharmacia CAP System. Allergy 2002; 57:423–30.10.1034/j.1398-9995.2002.13248.xSearch in Google Scholar PubMed

41. van Ree R, Antonicelli L, Akkerdaas JH, Garritani MS, Aalberse RC, Bonifazi F. Possible induction of food allergy during mite immunotherapy. Allergy 1996; 51:108–13.10.1111/j.1398-9995.1996.tb00043.xSearch in Google Scholar

42. Twardosz A, Hayek B, Seiberler S, Vangelista L, Elfman L, Gronlund H, et al. Molecular characterization, expression in Escherichia coli, and epitope analysis of a two EF-hand calcium-binding birch pollen allergen, Bet v 4. Biochem Biophys Res Commun 1997; 239:197–204.10.1006/bbrc.1997.6860Search in Google Scholar PubMed

43. Valenta R, Hayek B, Seiberler S, Bugajska-Schretter A, Niederberger V, Twardosz A, et al. Calcium-binding allergens: from plants to man. Int Arch Allergy Immunol 1998; 117:160–6.10.1159/000024005Search in Google Scholar PubMed

44. Tinghino R, Twardosz A, Barletta B, Eleonora MR, Puggioni BD, Iacovacci P, et al. Molecular, structural, and immunologic relationships between different families of recombinant calcium-binding pollen allergens. J Allergy Clin Immunol 2002; 109:314–20.10.1067/mai.2002.121528Search in Google Scholar PubMed

45. Verdino P, Westritschnig K, Valenta R, Keller W. The cross-reactive calcium-binding pollen allergen, Phl p 7, reveals a novel dimer assembly. EMBO J 2002; 21:5007–16.10.1093/emboj/cdf526Search in Google Scholar PubMed PubMed Central

46. Verdino P, Westritschnig K, Valenta R, Keller W. Three-dimensional structure of the panallergen Phl p 7. Int Arch Allergy Immunol 2003; 130:10–1.10.1159/000068378Search in Google Scholar

47. Andersson K, Lidholm J. Characteristics and immunobiology of grass pollen allergens. Int Arch Allergy Immunol 2003; 130:87–107.10.1159/000069013Search in Google Scholar

48. Niederberger V, Laffer S, Fröschl R, Kraft D, Rumpold H, Kapiotis M, et al. IgE antibodies to recombinant pollen allergens (Phl p 1, Phl p 2, Phl p 5, and Bet v 2) account for a high percentage of grass pollen-specific IgE. J Allergy Clin Immunol 1998; 101:258–64.10.1016/S0091-6749(98)70391-4Search in Google Scholar

49. Vrtala S, Fischer S, Grote M, Vangelista L, Pastore A, Sperr WR, et al. Molecular, immunological, and structural characterization of Phl p 6, a major allergen and P-particle-associated protein from timothy grass (Phleum pratense) pollen. J Immunol 1999; 163:5489–96.10.4049/jimmunol.163.10.5489Search in Google Scholar

50. Laffer S, Valenta R, Vrtala S, Susani M, van Ree R, Kraft D, et al. Complementary DNA cloning of the major allergen Phl p 1 from timothy grass (Phleum pratense): recombinant Phl p 1 inhibits IgE binding to group I allergens from eight different grass species. J Allergy Clin Immunol 1994; 94:689–98.10.1016/0091-6749(94)90176-7Search in Google Scholar

51. Kazemi-Shirazi L, Niederberger V, Linhart B, Lidholm J, Kraft D, Valenta R. Recombinant marker allergens: diagnostic gatekeepers for the treatment of allergy. Int Arch Allergy Immunol 2002; 127:259–68.10.1159/000057742Search in Google Scholar

52. Pittner G, Vrtala S, Thomas WR, Weghofer M, Kundi M, Horak F, et al. Component-resolved diagnosis of house-dust mite allergy with purified natural and recombinant mite allergens. Clin Exp Allergy 2004; 34:597–603.10.1111/j.1365-2222.2004.1930.xSearch in Google Scholar

53. Gronlund , H, Bergman T, Sandstrom K, Alvellus G, Reininger R, Verdino P, et al. Formation of disulfide bonds and homodimers of the major cat allergen Fel d 1 equivalent to the natural allergen by expression in Escherichia coli. J Biol Chem 2003; 278:40144–51.10.1074/jbc.M301416200Search in Google Scholar

54. Valenta R. Diagnostic tests based on recombinant allergens: assistance for the selection of allergy therapies. In Wall K, editor: New horizons – allergy, Vol 1. Uppsala, Sweden: Pharmacia Diagnostics AB, 2002:1–6.Search in Google Scholar

55. Westritschnig K, Kraft D, Valenta R. Rekombinante Allergene in der Diagnose der Typ I Allergie. J Lab Med 2002; 26:120–9.10.1111/j.1439-0477.2002.02039.pp.xSearch in Google Scholar

56. Valenta R, Ball T, Focke M, Linhart B, Mothes N, Niederberger V, et al. Immunotherapy of allergic disease. Adv Immunol 2004; 82:105–53.10.1016/S0065-2776(04)82003-0Search in Google Scholar

57. Jutel M, Pichler WJ, Skrbic D, Urwyler A, Dahinden C, Müller UR. Bee venom immunotherapy results in decrease of IL-4 and IL-5 and increase of IFN-γ secretion in specific allergen-stimulated T-cell cultures. J Immunol 1995; 154:4187–94.10.4049/jimmunol.154.8.4187Search in Google Scholar

58. Ebner C, Siemann U, Bohle B, Wilheim M, Wiedermann U, Schenk S, et al. Immunological changes during specific immunotherapy of grass pollen allergy: reduced lymphoproliferative responses to allergen and shift from TH2 to TH1 in T-cell clones specific for Phl p 1, a major grass pollen allergen. Clin Exp Allergy 1997; 27:1007–15.10.1111/j.1365-2222.1997.tb01252.xSearch in Google Scholar PubMed

59. Akdis CA, Blesken T, Akdis M, Wüthrich B, Blaser K. Role of interleukin 10 in specific immunotherapy. J Clin Invest 1998; 102:98–106.10.1172/JCI2250Search in Google Scholar

60. Van Ree R, Van Leeuwen WA, Dieges PH, Van Wijk RG, De Jong N, Brewczyski PZ, et al. Measurement of IgE antibodies against purified grass pollen allergens (Lol p 1, 2, 3 and 5) during immunotherapy. Clin Exp Allergy 1997; 27:68–74.10.1111/j.1365-2222.1997.tb00674.xSearch in Google Scholar

61. Bousquet J, Lockey R, Malling HJ and the WHO panel members. Allergen immunotherapy: therapeutic vaccines for allergic diseases: a WHO position paper. J Allergy Clin Immunol 1998; 102:558–62.10.1016/S0091-6749(98)70271-4Search in Google Scholar

62. Valenta R. The future of antigen-specific immunotherapy of allergy. Nat Rev Immunol 2002; 2:446–53.10.1038/nri824Search in Google Scholar PubMed

63. Valenta R, Kraft D. Recombinant allergen molecules: tools to study effector cell activation. Immunol Rev 2001; 179:119–27.10.1034/j.1600-065X.2001.790112.xSearch in Google Scholar

64. Vrtala S, Hirtenlehner K, Vangelista L, Pastore A, Eichler HG, Sperr WR, et al. Conversion of the major birch pollen allergen, Bet v 1, into two nonanaphylactic T cell epitope-containing fragments: candidates for a novel form of specific immunotherapy. J Clin Invest 1997; 99:1673–81.10.1172/JCI119330Search in Google Scholar PubMed PubMed Central

65. Ball T, Fuchs T, Sperr WR, Valent P, Vangelista L, Kraft D, et al. B cell epitopes of the major timothy grass pollen allergen, phl p 1, revealed by gene fragmentation as candidates for immunotherapy. FASEB J 1999; 13:1277–90.10.1096/fasebj.13.11.1277Search in Google Scholar PubMed

66. Valenta R, Vrtala S, Focke-Tejkl M, Bugalska-Schretter A, Ball T, Twardosz A, et al. Genetically engineered and synthetic allergen dervatives: candidates for vaccination against type l allergy. Biol Chem 1999; 380:815–24.10.1515/BC.1999.101Search in Google Scholar PubMed

67. Bhalla PL, Swoboda I, Singh MB. Reduction in allergenicity of grass pollen by genetic engineering. Int Arch Allergy Immunol 2001; 124:51–4.10.1159/000053666Search in Google Scholar PubMed

68. Vrtala S, Hirtenlehner K, Vangelista L, Pastore A, Eichler HG, Sperr WR, et al. Division of the major birch pollen allergen, Bet v 1, into two non-anaphylactic fragments. Int Arch Allergy Immunol 1997; 113:246–8.10.1159/000237560Search in Google Scholar PubMed

69. Lowenstein H, Spacholt SH, Klysner SS, Ipsen H, Larsen JN. The significance of isoallergenic variations in present and future specific immunotherapy. Int Arch Allergy Immunol 1995; 107:285–9.10.1159/000237004Search in Google Scholar

70. Breiteneder H, Ferreira F, Hoffmann-Sommergruber K, Ebner C, Breitenbach M, Rumpold H, et al. Four recombinant isoforms of Cor a I, the major allergen of hazel pollen, show different IgE-binding properties. Eur J Biochem 1993; 212:355–62.10.1111/j.1432-1033.1993.tb17669.xSearch in Google Scholar

71. Ferreira F, Hirtenlehner K, Jilek A, Godnik-Cvar J, Breiteneder H, Grimm R, et al. Dissection of immunoglobulin E and T lymphocyte reactivity of isoforms of the major birch pollen allergen Bet v 1: potential use of hypoallergenic isoforms for immunotherapy. J Exp Med 1996; 183:599–609.10.1084/jem.183.2.599Search in Google Scholar

72. Vrtala S, Hirtenlehner K, Susani M, Akdis M, Kussebi F, Akdis CA, et al. Genetic engineering of a hypoallergenic trimer of the major birch pollen allergen Bet v 1. FASEB J 2001; 15:2045–7.10.1096/fj.00-0767fjeSearch in Google Scholar

73. Linhart B, Jahn-Schmid B, Verdino P, Keller W, Ebner C, Kraft D, et al. Combination vaccines for the treatment of grass pollen allergy consisting of genetically engineered hybrid molecules with increased immunogenicity. FASEB J 2002; 16:1301–3.10.1096/fj.01-1012fjeSearch in Google Scholar

74. Niederberger V, Stubner P, Spitzauer S, Kraft D, Valenta R, Ehrenberger K, et al. Skin test results but not serology reflect immediate type respiratory sensitivity: a study performed with recombinant allergen molecules. J Invest Dermatol 2001; 117:848–51.10.1046/j.0022-202x.2001.01470.xSearch in Google Scholar

75. Heiss S, Mahler V, Steiner R, Spitzauer S, Schweiger C, Kraft D, et al. Component-resolved diagnosis (CRD) of type I allergy with recombinant grass and tree pollen allergens by skin testing. J Invest Dermatol 1999; 113:830–7.10.1046/j.1523-1747.1999.00796.xSearch in Google Scholar

76. Tresch S, Holzmann D, Baumann S, Blaser K, Wuthrich B, Crameri R, et al. In vitro and in vivo allergenicity of recombinant Bet v 1 compared to the reactivity of natural birch pollen extract. Clin Exp Allergy 2003; 33:1153–8.10.1046/j.1365-2222.2003.01717.xSearch in Google Scholar

77. Arquint O, Helbling A, Crameri R, Ferreira F, Breitenbach M, Pichler WJ. Reduced in vivo allergenicity of Bet v 1d isoform, a natural component of birch pollen. J Allergy Clin Immunol 1999; 104:1239–43.10.1016/S0091-6749(99)70019-9Search in Google Scholar

78. van Hage-Hamsten M, Kronqvist M, Zetterström O, Johansson E, Niederberger V, Vrtala S, et al. Skin test evaluation of genetically engineered hypoallergenic derivatives of the major birch pollen allergen, Bet v 1. Results obtained with a mix of two recombinant Bet v 1 fragments and rBet v 1 trimer in a Swedish population before the birch pollen season. J Allergy Clin Immunol 1999; 104:969–77.10.1016/S0091-6749(99)70077-1Search in Google Scholar

79. Pauli G, Purohit A, Oster JP, de Blay F, Vrtala S, Niederberger V, et al. Comparison of genetically engineered hypoallergenic rBet v 1 derivatives by skin prick and intradermal testing: results obtained in a French population. Clin Exp Allergy 2000; 30:1076–84.10.1046/j.1365-2222.2000.00869.xSearch in Google Scholar PubMed

80. Nopp A, Halden G, Lundhal J, Johansson E, Vrtala S, Valenta R, et al. Comparison of inflammatory responses to genetically engineered hypoallergenic derivatives of the major birch pollen allergen, Bet v 1, induces less eosinophilic activity in skin chamber fluids collected from birch pollen allergic patients than rBet v 1 wild type. J Allergy Clin Immunol 2000; 106:101–9.10.1067/mai.2000.106924Search in Google Scholar PubMed

81. Kauppinen J, Zeiler T, Rautiainen J, Rytkonen-Nissinen M, Taivainen A, Mantyjarvi R, et al. Mutant derivatives of the main respiratory allergen of cow are less allergenic than the intact molecule. Clin Exp Allergy 1999; 29:989–96.10.1046/j.1365-2222.1999.00605.xSearch in Google Scholar PubMed

82. Kronqvist M, Johansson E, Whitley P, Olsson S, Gafvelin G, Scheynius A, et al. A hypoallergenic derivative of the major allergen of the dust mite Lepidoglyphus destructor, Lep d 2.6Cys, induces less IgE reactivity and cellular response in the skin than recombinant Lep d 2. Int Arch Allergy Immunol 2001; 126:41–9.10.1159/000049493Search in Google Scholar PubMed

83. Bonura A, Amoroso S, Locorotondo G, Di Felice G, Tinghino R, Geraci D, et al. Hypoallergenic variants of the Parietaria judaica major allergen Par j 1: a member of the non-specific lipid transfer protein plant family. Int Arch Allergy Immunol 2001; 126:32–40.10.1159/000049492Search in Google Scholar PubMed

Published Online: 2006-2-13
Published in Print: 2006-2-1

©2006 by Walter de Gruyter Berlin New York

Articles in the same Issue

  1. Allergy testing: the role of recombinant allergens
  2. Autoimmune diagnostics in diabetes mellitus
  3. Diagnosis and prognosis of early rheumatoid arthritis, with special emphasis on laboratory analysis
  4. Autoimmune bullous disorders
  5. Laboratory network of excellence: enhancing patient safety and service effectiveness
  6. Novel mutations in the 5′-UTR of the FOLR1 gene
  7. CYP2C8 polymorphism among the Portuguese
  8. Actual levels of soy phytoestrogens in children correlate with thyroid laboratory parameters
  9. Comparison of the concentration of trace metals (Ni, Zn, Co, Cu and Se), Fe, vitamins A, C and E, and lipid peroxidation in patients with prostate cancer
  10. Comparison of Brucella immunoglobulin M and G flow assays with serum agglutination and 2-mercaptoethanol tests in the diagnosis of brucellosis
  11. Experimental and computer modelling speciation studies of the effect of pH and phosphate on the precipitation of calcium and magnesium salts in urine
  12. Total tau protein, phosphorylated tau (181p) protein, β-amyloid1–42, and β-amyloid1–40 in cerebrospinal fluid of patients with dementia with Lewy bodies
  13. Establishment of an indocyanine green test using an automatic chemistry analyzer
  14. Relationship between serum sialic acids, sialic acid-rich inflammation-sensitive proteins and cell damage in patients with acute myocardial infarction
  15. Ischemia-modified albumin and NT-prohormone-brain natriuretic peptide in peripheral arterial disease
  16. Nitration of human plasminogen by RAW 264.7 macrophages reduces streptokinase-induced plasmin activity
  17. Comparison of triglyceride concentration with lipemic index in disorders of triglyceride and glycerol metabolism
  18. Measurement of glycated hemoglobin (HbA1c) with an automated POCT instrument in comparison with HPLC and automated immunochemistry method: evaluation of the influence of hemoglobin variants
  19. Analytical performance and clinical efficacy for cardiovascular risk estimation of an Olympus immunoturbidimetric high-sensitivity C-reactive protein assay
  20. Systemic matrix metalloproteinase-9 (MMP-9) levels as prognostic indexes of bone disease in patients with multiple myeloma
  21. Systemic levels of matrix metalloproteinase-9 in patients with multiple myeloma may be useful as a prognostic index of bone disease. Reply to the Letter by Demacq and Montenegro
  22. Society of Medical Biochemists of Serbia and Montenegro: 50-year anniversary
Downloaded on 7.2.2026 from https://www.degruyterbrill.com/document/doi/10.1515/CCLM.2006.024/pdf
Scroll to top button