k219 rHev b 6.01 Latex

Allergens within Occupational Allergens

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  • Latin name: Hevea brasiliensis
  • Common names: Prohevein (hevein precursor)
  • Source material: Recombinant non-glycosylated MBP fusion protein produced in an E. coli strain carrying a cloned cDNA encoding Hevea brasiliensis allergen Hev b 6.01.
Recombinant allergen
Hevea brasiliensis allergen Hev b 6.01
 
Biological function
Class I endochitinase containing a hevein domain.

Mw
20 kDa
 
Allergen description
Hev b 6.01 (1-2), prohevein, is one of the most important Latex allergens in health care worker (HCW) Latex allergy. Prohevein, Hev b 6.01, is processed to yield 2 allergenic fragments, the N-terminal hevein, Heb b 6.02, and the C-terminal portion, Hev b 6.03 (3-4). All 3 allergens exist in the plant, although the ratio between Hev b 6.01 and Hev b 6.03 is about 30:1 (5). All 3 components act as independent allergens (2). Hevein comprises the most important part of IgE-binding epitopes in the prohevein molecule.
 
Hev b 6.01 was reported to be recognised by 88.9% of 54 Latex-allergic patients (6). Other studies have reported a prevalence of between 70-86% sensitisation to this allergen in Latex-allergic individuals (1, 7).
 
In a study of Latex-allergic patients, prohevein bound IgE from sera of 15 of 20 (75%) patients, and the prohevein C-domain bound 3 of 20 (15%) Latex-allergic patient sera. In ELISA, 36 of 52 (69%) patient sera showed IgE binding to prohevein, whereas 11 of 52 (21%) sera had IgE antibodies to the prohevein C-domain. Purified hevein inhibited 72% of IgE binding from pooled sera of Latex-allergic patients to solid phase glove extract and 45% of IgE binding to solid phase Natural rubber latex (NRL) (8).
 
The recombinant allergen has allergenic activity very similar to that of native Hev b 6.01. Seventeen of 18 (94%) serum samples from Latex-allergic HCW showed increased levels of allergen-specific IgE to rHev b 6.01, 16 (89%) to rHev b 6.02, and 13 (72%) to rHev b 6.03 in a study evaluating recombinant Hev b 6 allergens. In the Hev b 6.01 precursor, the regions responsible for IgE binding and those for inducing the T-cell proliferation responses are settled in different parts of the protein. The Hev b 6.02 domain is responsible for IgE binding and carries discontinuous B-cell epitopes, whereas Hev b 6.03 is a better inducer of a proliferation response and contains HLADR4- binding motifs (2).
 
Individuals with NRL allergy often have immediate reactions to plant-derived foods and fresh fruits, such as Avocado and Banana. More than 50% of subjects having IgE-mediated NRL allergy are reported to be sensitised to Avocado, as demonstrated by allergen-specific IgE. About 10-20% report hypersensitivity reactions after ingesting Avocado. The conserved hevein domain of the major Latex allergen prohevein (Hev b 6.01) is a ubiquitous chitin-binding protein structure that can be found in several plant proteins and may be responsible for the observed cross-reactivity between Latex and Avocado.
 
Sensitisation to endochitinase class I containing a hevein domain is the main underlying pathomechanism in Latex-mediated Avocado allergy (9). In a study evaluating skin testing against purified proteins in 15 patients with NRL allergy, 11 (73%) patients were found to have reactivity to isolated hevein-like domains of Avocado and Banana, but only 1 (7%) patient reacted to their corresponding endochitinases. Proteins from Avocado and Banana inhibited binding of IgE antibodies to prohevein (Hev b 6.01) in 59% and 38% of patients, respectively (10). Other studies have also identified this as the panallergen responsible (11). In immunoblotting studies, sera of 9 of 15 patients allergic to NRL with IgE antibodies to hevein also demonstrated specific IgE binding to 32- and 33-kDa Banana proteins (12). Similarly, in a patient who experienced an anaphylactic reaction to Apple juice containing acerola, cross-reactivity with Latex due to prohevein was demonstrated (13).

References:

    1. Rozynek P, Posch A, Baur X. Cloning, expression and characterization of the major latex allergen prohevein. Clin Exp Allergy 1998;28(11):1418-26.
    2. Raulf-Heimsoth M, Rozynek P, Bruning T, Rihs HP. Characterization of B- and T-cell responses and HLA-DR4 binding motifs of the latex allergen Hev b 6.01 (prohevein) and its post-transcriptionally formed proteins Hev b 6.02 and Hev b 6.03. Allergy 2004;59(7):724-33.
    3. Sussman GL, Beezhold DH, Kurup VP. Allergens and natural rubber proteins. J Allergy Clin Immunol 2002;110(2 Pt 2):S033-9.
    4. de Silva HD, Gardner LM, Drew AC, Beezhold DH, Rolland JM, O'Hehir RE. The hevein domain of the major latex-glove allergen Hev b 6.01 contains dominant T cell reactive sites. Clin Exp Allergy 2004;34(4):611-8.
    5. Yeang HY, Arif SA, Yusof F, Sunderasan E. Allergenic proteins of natural rubber latex. Methods 2002;27(1):32-45.
    6. Chardin H, Raulf-Heimsoth M, Chen Z, Rihs HP, Mayer C, Desvaux FX, Senechal H, Peltre G. Interest of two-dimensional electrophoretic analysis for the characterization of the individual sensitization to latex allergens. Int Arch Allergy Immunol 2002;128(3):195-203.
    7. Drew AC, Eusebius NP, Kenins L, de Silva HD, Suphioglu C, Rolland JM, O'hehir RE. Hypoallergenic variants of the major latex allergen Hev b 6.01 retaining human T lymphocyte reactivity. J Immunol 2004;173(9):5872-9.
    8. Alenius H, Kalkkinen N, Reunala T, Turjanmaa K, Palosuo T. The main IgE-binding epitope of a major latex allergen, prohevein, is present in its N-terminal 43-amino acid fragment, hevein. J Immunol 1996;156(4):1618-25.
    9. Posch A, Wheeler CH, Chen Z, Flagge A, Dunn MJ, Papenfuss F, Raulf-Heimsoth M, Baur X. Class I endochitinase containing a hevein domain is the causative allergen in latex-associated avocado allergy. Clin Exp Allergy 1999;29(5):667-72.
    10. Karisola P, Kotovuori A, Poikonen S, Niskanen E, Kalkkinen N, Turjanmaa K, Palosuo T, Reunala T, Alenius H, Kulomaa MS. Isolated hevein-like domains, but not 31-kd endochitinases, are responsible for IgE-mediated in vitro and in vivo reactions in latex-fruit syndrome. J Allergy Clin Immunol 2005;115(3):598-605.
    11. Diaz-Perales A, Blanco C, Sanchez-Monge R, Varela J, Carrillo T, Salcedo G. Analysis of avocado allergen (Prs a 1) IgE-binding peptides generated by simulated gastric fluid digestion. J Allergy Clin Immunol 2003;112(5):1002-7.
    12. Mikkola JH, Alenius H, Kalkkinen N, Turjanmaa K, Palosuo T, Reunala T. Hevein-like protein domains as a possible cause for allergen cross-reactivity between latex and banana. J Allergy Clin Immunol 1998;102(6 Pt 1):1005-12.
    13. Raulf-Heimsoth M, Stark R, Sander I, Maryska S, Rihs HP, Bruning T, Voshaar T. Anaphylactic reaction to apple juice containing acerola: cross-reactivity to latex due to prohevein. J Allergy Clin Immunol 2002;109(4):715-6.

2006



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