t215 rBet v 1 PR-10, Birch

Allergens within Tree Pollens

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  • Latin name: Betula verrucosa
  • Common names: PR-10 protein
  • Source material: Recombinant non-glycosylated protein produced in an E. coli strain carrying a cloned cDNA encoding Betula verrucosa allergen Bet v 1.
Recombinant Allergen
Betula verrucosar allergen Bet v 1.

Biological function
IPR-proteins, ribonucleases (1).
 
Mw  
17 kDa.
 
Other allergens isolated
rBet v 1a and rBet v 1d isoforms. These isoforms differ in their ability
to bind IgE but are similar in their immunogenicity for T cells (2-3).
 
Allergen description
The major allergen of birch tree pollen is Bet v (4-22). Recombinant Bet v 1 was among the first allergen-encoding cDNAs isolated and has significant sequence homology to a group of pathogenesis-related plant proteins and has been classified as a PR-10 protein Recombinant Bet v 1 has been shown to bind IgE in most birch-pollen allergic patients (20-22).  In one study, the accuracy of in vivo and in vitro diagnosis of birch pollen allergy by means of rBet v 1 was > 95% (49/51) (22). Nevertheless, differences in IgE antibody reactivity to rBet v 1 and rBet v 2 were demonstrated among allergic patients from 6 countries. The complexity of reactivity tended to be greater in individuals from the central and southern parts of Europe than from Sweden and Finland (23).
 
Several cross-reactive Bet v 1-homologoues are major allergens of Fagales pollen (Alder, Hazel, Hornbeam) and taxonomically related fruits, vegetables, and spices (e.g., Carrot, Celery, Apple, Apricot, Cherry, and Pear). This seems to be clearly related to the clinical pollen/food cross-reactivity found in oral allergy syndrome (OAS) (22, 24). Studies have suggested that Bet v 1 is the initial sensitising allergen in many cases of Fagales pollen allergy and Birch pollen-related plant-food allergy (OAS) at least in areas where birch trees are common, as in Northern Europe (22, 24). Population studies affirm that Bet v 1 is a marker allergen for genuine sensitisation to Fagales pollen- and Birch pollen-related food allergy (22, 24-25).
 
Bet v 1 is recognised by IgE antibodies from about 95%of Birch-allergic patients Bet v 2 and Bet v 3 from 10% and Bet v 6 by approximately 32% (26). The sensitisation profiles to Bet v 1 and Bet v 2 differ among geographical areas. Bet v 2, a profilin and a minor allergen, has also been shown to be involved in cross-reactivity to certain foods.
 
It has been suggested that Bet v 1 can be a diagnostic marker allergen for identifying patients with genuine sensitisation to birch-pollen (27), whereas more highly cross-reactive allergens, such as Bet v 2 and Bet v 4, may serve as marker allergens for syndromes involving cross-reactivity with unrelated plants/plant products (27-28). Accordingly, patients who exhibit positive skin tests to birch pollen extracts but have never been exposed to Birch might be considered to have IgE antibodies to cross-reactive allergens such as profilin (28). Therefore, the use of rBet v 1 to identify patients with genuine birch pollen sensitisation and to confirm the diagnosis of birch pollen allergy before initiating immunotherapy with birch pollen extract has been recommended (28).
 
One example of a diagnostic application of recombinant birch allergens is found in a study examining allergen-specific serum IgE antibodies using the recombinant allergens Bet v 1, Bet v 2 and Bet v 4, as examined in birch-sensitive patients from the province of Cuneo, in northwestern Italy. It was reported that of 372 patients, 215 (58%) had serum IgE antibodies to Bet v 1, 166 (45%) to Bet v 2, and 35 (9%) to Bet v 4. Monosensitisation to Bet v 1 occurred in 146 (39%) of patients; in 96 (26%) to Bet v 2; and in only 4 (1%) to Bet v 4. Thirty-nine sera (11%) did not contain allergen-specific IgE antibodies to any of these three individual birch pollen allergens. All 372 sera (100%) had IgE antibodies against natural Birch pollen extract; 162 (44%) contained IgE antibodies reacting with Apple extract (75% of Bet v 1 positive sera). The study concluded that the 3 recombinant birch pollen allergens alone could identify 90% of birch pollen-sensitive patients (7).

References:

    1. www.allergome.org
    2. 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(6):1239-43.
    3. Spangfort MD, Ipsen H, Sparholt SH, Aasmul-Olsen S, Osmark P, Poulsen FM, Larsen M, Mortz E, Roepstorff P, Larsen JN. Characterisation of recombinant isoforms of birch pollen allergen Bet v 1. Adv Exp Med Biol 1996;409:251-4.
    4. Mahler V, Vrtala S, Kuss O, Diepgen TL, Suck R, Cromwell O, Fiebig H, Hartl A, Thalhamer J, Schuler G, Kraft D, Valenta R. Vaccines for birch pollen allergy based on genetically engineered hypoallergenic derivatives of the major birch pollen allergen, Bet v 1. Clin Exp Allergy 2004 Jan;34(1):115-22.
    5. De Amici M, Mosca M, Vignini M, Quaglini S, Moratti R. Recombinant birch allergens (Bet v 1 and Bet v 2) and the oral allergy syndrome in patients allergic to birch pollen. Ann Allergy Asthma Immunol 2003 Nov;91(5):490-2.
    6. Tresch S, Holzmann D, Baumann S, Blaser K, Wuthrich B, Crameri R, Schmid-Grendelmeier P. 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(8):1153-8.
    7. Rossi RE, Monasterolo G, Monasterolo S. Detection of specific IgE antibodies in the sera of patients allergic to birch pollen using recombinant allergens Bet v 1, Bet v 2, Bet v 4: evaluation of different IgE reactivity profiles. Allergy 2003 ;58(9):929-32.
    8. Kaul S, Scheurer S, Danz N, Schicktanz S, Vieths S, Hoffmann A. Monoclonal IgE antibodies against birch pollen allergens: novel tools for biological characterization and standardization of allergens. J Allergy Clin Immunol 2003 Jun;111(6):1262-8.
    9. Vrtala S, Hirtenlehner K, Susani M, Akdis M, Kussebi F, Akdis CA, Blaser K, Hufnagl P, Binder BR, Politou A, Pastore A, Vangelista L, et al. Genetic engineering of a hypoallergenic trimer of the major birch pollen allergen Bet v 1. FASEB J 2001;15(11):2045-7.
    10. Pauli G, Purohit A, Oster JP, de Blay F, Vrtala S, Niederberger V, Kraft D, Valenta R. Skin testing with wild-type recombinant birch pollen allergens and hypoallergenic modified molecules. Arb Paul Ehrlich Inst Bundesamt Sera Impfstoffe Frankf A M. 1999;(93):203-10.
    11. Pauli G, Purohit A, Oster JP, De Blay F, Vrtala S, Niederberger V, Kraft D, Valenta R. Comparison of genetically engineered hypoallergenic rBet v 1 derivatives with rBet v 1 wild-type by skin prick and intradermal testing: results obtained in a French population. Clin Exp Allergy 2000;30(8):1076-84.
    12. Diez-Gomez ML, Quirce S, Cuevas M, Sanchez-Fernandez C, et al. Fruit-pollen-latex cross-reactivity: implication of profilin (Bet v 2). Allergy 1999;54(9):951-61.
    13. Pauli G, Purohit A, Oster JP, de Blay F, Vrtala S, Niederberger V, Kraft D, Valenta R. Clinical evaluation of genetically engineered hypoallergenic rBet v 1 derivatives. Int Arch Allergy Immunol 1999;118(2-4):216-7.
    14. Niederberger V, Pauli G, Gronlund H, Froschl R, Rumpold H, et al. Recombinant birch pollen allergens (rBet v 1 and rBet v 2) contain most of the IgE epitopes present in birch, alder, hornbeam, hazel, and oak pollen: a quantitative IgE inhibition study with sera from different populations. J Allergy Clin Immunol 1998;102(4 Pt 1):579-91.
    15. Godnic-Cvar J, Susani M, Breiteneder H, Berger A, Havelec L, Waldhor T, Hirschwehr R, Valenta R, Scheiner O, Rudiger H, Kraft D, Ebner C. Recombinant Bet v 1, the major birch pollen allergen, induces hypersensitivity reactions equal to those induced by natural Bet v 1 in the airways of patients allergic to tree pollen. J Allergy Clin Immunol 1997;99(3):354-9.
    16. Hoffmann-Sommergruber K, Susani M, Ferreira F, Jertschin P, Ahorn H, Steiner R, Kraft D, Scheiner O, Breiteneder H. High-level expression and purification of the major birch pollen allergen, Bet v 1. Protein Expr Purif 1997;9(1):33-9.
    17. Menz G, Dolecek C, Schonheit-Kenn U, Ferreira F, Moser M, Schneider T, Suter M, Boltz-Nitulescu G, Ebner C, Kraft D, Valenta R. Serologic and skin test diagnosis of birch pollen allergy with recombinant Bet v 1, the chief allergen of birch. [German] Pneumologie 1996;50(9):632-40.
    18. Ferreira FD, Hoffmann-Sommergruber K, Breiteneder H, et al. Purification and characterization of recombinant Bet v I, the major birch pollen allergen. Immunological equivalence to natural Bet v I. J Biol Chem 1993;268(26):19574-80.
    19. Larsen JN, Casals AB, From NB, Stroman P, Ipsen H. Characterization of recombinant bet vI, the major pollen allergen of Betula verrucosa (white birch), produced by fed-batch fermentation. Int Arch Allergy Immunol 1993;102(3):249-58.
    20. Vrtala S, Hirtenlehner K, Susani M, Hufnagl P, Binder BR, Vangelista L, Pastore A, Sperr WR, Valent P, Ebner C, Kraft D, Valenta R. Genetic engineering of recombinant hypoallergenic oligomers of the major birch pollen allergen, Bet v 1: candidates for specific immunotherapy. Int Arch Allergy Immunol 1999;118(2-4):218-9.
    21. Valenta R, Duchene M, Vrtala S, Birkner T, Ebner C, Hirschwehr R, Breitenbach M, et al. Recombinant allergens for immunoblot diagnosis of tree-pollen allergy. J Allergy Clin Immunol 1991;88(6):889-94.
    22. Menz G, Dolecek C, Schonheit-Kenn U, Ferreira F, Moser M, Schneider T, Suter M, Boltz-Nitulescu G, Ebner C, Kraft D, Valenta R. Serological and skin-test diagnosis of birch pollen allergy with recombinant Bet v I, the major birch pollen allergen. Clin Exp Allergy 1996;26(1):50-60.
    23. Elfman L, Svensson M, Lidholm J, Pauli G, Valenta R. Different profiles in specific IgE to rBet v 1 and rBet v 2 in patients allergic to birch pollen from six countries. Int Arch Allergy Immunol 1997;113(1-3):249-51.
    24. Kazemi-Shirazi L, Pauli G, Purohit A, Spitzauer S, Froschl R, Hoffmann-Sommergruber K, Breiteneder H, Scheiner O, Kraft D, Valenta R. Quantitative IgE inhibition experiments with purified recombinant allergens indicate pollen-derived allergens as the sensitizing agents responsible for many forms of plant food allergy. J Allergy Clin Immunol 2000;105(1 Pt 1):116-25.
    25. Moverare R, Westritschnig K, Svensson M, Hayek B, Bende M, Pauli G, Sorva R, Haahtela T, Valenta R, Elfman L. 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(4):325-35.
    26. Karamloo F, Schmitz, N, Scheurer S, et al. Molecular cloning and characterization of a birch pollen minor allergen, Bet v 5, belonging to a family of isoflavone reductase-related proteins. J Allergy Clin Immunol 1999;104:991-999.
    27. 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(4):259-68.
    28. Mothes N, Valenta R. Biology of tree pollen allergens. Curr Allergy Asthma Rep 2004;4(5):384-90.

2006



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