Rt225 rBet v 6 Birch

Allergens within Tree Pollens

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  • Latin name: Betula verrucosa
  • Common names: IFR, Isoflavone reductase, (PCBER)
  • Source material: Allergen source material: An E. coli strain carrying a cloned cDNA encoding Betula verrucosa allergen Bet v 6
Recombinant allergen
Betula verrucosa allergen Bet v 6.
 
Biological function
Bet v 6 is a Isoflavone reductase (1).
 
Mw
35 kDa.
 
Allergen description
Bet v 6, a minor Birch pollen allergen, is an isoflavone reductase (IFR). IFRs have been found in apple, pear, orange, mango, lychee, carrots, bananas, peas and chickpeas (1). An IFR-like protein has also been isolated from maize and tobacco (1, 2). IFR has been demonstrated in legumes and alfalfa, and a IFR-like protein had been documented in maize (3-4). The laboratory and clinical relevance of IFRs in other plants has yet to be determined.
 
Birch IFR has a sequence identity of 56% to 80% to IFR homologues proteins from various plants (1). The IFRs are plant defense proteins and appear to be induced by plant stress. A gene that is selectively induced both in roots and shoots in response to sulfur starvation has been demonstrated (3). The role of plant stress in the induction of IFRs is demonstrated by grapefruit, which when treated to induce resistance against the mould decay, produced an isoflavone reductase-like protein which had a high homology to other isoflavone reductase-like proteins present in non-legume plants (5).
 
Isoflavone reductase (IFR) belongs to a family of plant proteins collectively termed as phenylcoumaran benzylic ether reductases (PCBERs) based on demonstrated catalytic activity. Bet v 6 displays a high degree of sequence identity of up to 81% with isoflavone reductase-homologous proteins (IFRH) and phenylcoumaran benzylic ether reductase (PCBER) as well as lower identities of 60% and 51% with isoflavone reductases (IFR) and pinoresinol-lariciresinol reductase (PLR), respectively. These reductases (IFR, IFRH, PCBER and PLR) all appear to be evolutionary derived from a common ancestor and each catalyzes a rather similar conversion in the isoflavonoid and lignan pathways.

Although the precise biochemical products so formed differ in each case, products of each reductase appear to be employed in plant defense. However, antibodies raised against PCBER do not cross-react with PLR (6-9). A characteristic difference between PCBER and isoflavone reductases (IFR) appears to be a 10 amino-acid insertion that is not present in PCBER, PLR and IFRH (8).
 
Bet v 6 has been found to share an 80% amino-acid sequence identity with Pyr c 5, a Bet v 6-related food allergen from pear. Assays with recombinant Pyr c 5 from Pear and Bet v 6 showed PCBER catalytic activity for both recombinant allergens, and both allergens had similar IgE binding characteristics and bound IgE from sera of birch-pollen-allergic and pear-allergic subjects. Inhibition experiments with Pyr c 5 suggested that homologous allergens may be present in many vegetable foods such as apple, peach, orange, lychee fruit, strawberry, persimmon, zucchini (courgette), and carrot. Laboratory tests of the recombinant Pyr c 5 using sera of a pear-allergic subject suggested that Pyr c 5 had the potential to elicit type I allergic reactions. This study’s data was reported to indicate that PCBER and IFR may represent a new family of pollen-related food allergens that occur not only in typical birch-pollen-related foods, but also in rarely allergenic fruits and vegetables such as orange, strawberry, persimmon, or zucchini (10-11).
 
Bet v 6 may be responsible for pollen-related oral allergy to specific foods in a minority of patients with birch pollen allergy (1). Bet v 6 is recognized by IgE from approximately 32% of Birch pollen allergic individuals. Recombinant Bet v 6 bound IgE from 32% of 28 sera from patients allergic to birch pollen with a CAP class of at least 3 compared to Bet v 1 binding in 89% of these patients (1).
 
Japanese cedar pollen, a major cause of seasonal pollinosis in Japan where more than 10% of Japanese people are affected, was shown to contain an isoflavone reductase-like protein. In contrast to Bet v 6 being reported as a minor allergen, this recombinant protein exhibited an IgE binding frequency of 76% (19/25) in Japanese cedar pollen allergic patients (12).
 
Allergy to Sharon fruit (persimmon) has been only rarely reported. Cross-reactivity with pollen (profilin, Bet v 1 and Bet v 6) appears to be involved. In a study of two patients with allergic reactions on first exposure to Sharon fruit, as well as 7 patients with birch-pollen-related apple allergy, found that an open challenge with Sharon fruit in 7 patients allergic to Birch pollen and Apple, who had not eaten Sharon fruit previously, was positive in 6/7 cases. The study concluded that Birch-pollen-related allergy to Sharon fruit is mediated by the known cross-reactive pollen allergens including Bet v 1 (13).

References:

    1. 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.
    2. Vieths S, Frank E, Scheurer S, Meyer HE, Hrazdina G, Haustein D. Characterization ofa new IgE-binding 35-kDa protein from birchpollen with cross-reacting homologues invarious plant foods. Scand J Immunol 1998;47(3):263-7.
    3. Petrucco S, Bolchi A, Foroni C, Percudani R, Rossi GL, Ottonello S. A maize geneencoding an NADPH binding enzyme highly homologous to isoflavone reductases isactivated in response to sulfur starvation. Plant Cell 1996;8(1):69-8051.
    4. Paiva NL, Edwards R, Sun YJ, Hrazdina G, Dixon RA. Stress responses in alfalfa (Medicago sativa L.) 11. Molecular cloningand expression of alfalfa isoflavone reductase, a key enzyme of isoflavonoid phytoalexin biosynthesis. Plant Mol Biol 1991;17(4):653-67.
    5. Lers A, Burd S, Lomaniec E, Droby S, Chalutz E. The expression of a grapefruit gene encoding an isoflavone reductase-likeprotein is induced in response to UV irradiation. Plant Mol Biol 1998;36(6):847-56.
    6. Gang DR, Kasahara H, Xia ZQ, VanderMijnsbrugge K, Bauw G, Boerjan W, VanMontagu M, Davin LB, Lewis NG. Evolution of plant defense mechanisms. Relationships of phenylcoumaran benzylic ether reductases to pinoresinol-lariciresinol and isoflavone reductases. J Biol Chem 1999 Mar12;274(11):7516-27.
    7. Gang DR, Dinkova-Kostova AT, Davin LB,Lewis NG. Phylogenetic links in plant defense systems: lignans, isoflavonoids and their reductases.  In Phytochemical  PestControl. Agents (Hedin, P.A., Hollingworth,R.M., Masler, E.P., Miyamoto, J. &Thompson, D.G., eds) American ChemicalSociety, Washington, DC 1997;658:58-89.55.
    8. Karamloo F, Wangorsch A, Kasahara H,Davin LB, Haustein D, Lewis NG, Vieths S.Phenylcoumaran benzylic ether andisoflavonoid reductases are a new class of cross-reactive allergens in birch pollen, fruits and vegetables. Eur J Biochem2001;268(20):5310-2056.
    9. Dinkova-Kostova AT, Gang DR, Davin LB,Bedgar DL, Chu A, Lewis NG.  (1996) (+)-Pinoresinol/(+)-lariciresinol reductase from Forsythia intermedia: protein purification, cDNA cloning, heterologous expression and comparison to isoflavone reductase. J Biol Chem 1996;271:29473-2948257.
    10. Wiedemann P, Giehl K, Almo SC, Fedorov AA, Girvin M, Steinberger P, Rudiger M, Ortner M, Sippl M, Dolecek C, Kraft D, Jockusch B, Valenta R. Molecular and structural analysis of a continuous birch profilin epitope defined by a monoclonal antibody. J Biol Chem 1996;271(47):29915-21.
    11. Vieths S, Scheurer S, Ballmer-Weber B.Current understanding of cross-reactivity of food allergens and pollen. Ann N Y Acad Sci 2002;964:47-6858.
    12. Kawamoto S, Fujimura T, Nishida M, TanakaT, Aki T, Masubuchi M et al. Molecular cloning and characterization of a new Japanese cedar pollen allergen homologous to plant isoflavone reductase family.Clin Exp Allergy 2002;32(7):1064-7059.
    13. Bolhaar ST, van Ree R, Ma Y, Bruijnzeel-Koomen CA, Vieths S, Hoffmann-Sommergruber K, Knulst AC, Zuidmeer L. Severe Allergy to Sharon Fruit Caused by Birch Pollen. Int Arch Allergy Immunol2004;136(1):45-52

2006



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