Cross-reactivity of Food Allergens with Latex – Diagnostic and Clinical Implications

Considerable efforts have been undertaken to characterise the molecular features of Hevea brasiliensis latex allergens as a result of the high prevalence of latex allergy in well-defined risk groups such as health-care workers (HCW) and children with spina bifida (SB). Most of the latex allergens have been purified to homogeneity by conventional purification methods or by molecular cloning techniques. The clear advantage of recombinant proteins in contrast to native proteins is that it is possible to produce large-scale quantities at high reproducible quality. Several latex allergens have sequence homology to other allergens (like chitinases, enolase, profilin, patatin-like protein) while others are unique and do not share any similarity. Some of these allergens are responsible for the so called 'latex-fruit syndrome'. With the knowledge and use of the single allergens it is possible to improve the in vivo and in vitro diagnosis and establish a component-resolved diagnostic approach as prerequisite for specific immunotherapy strategies. This paper was delivered by Priv. Doz. Dr. Monika Raulf-Heimsoth at the Combined Congress of the South African Thoracic Society (SATS), Allergy Society of South Africa (ALLSA) and the South African Cystic Fibrosis Association held on 2-5 March 2007 at the Cape Town International Convention Centre. Dr RaulfHeimsoth received an ALLSA honorary membership award for her contribution towards promoting occupational allergy research in South Africa. with rHev b 5 has been shown to be an improvement on the in vitro test for an IgE-related sensitisation. Important NRL allergens, such as Hev b 2 and Hev b 13, are glycolysated proteins. Hev b 2, for example, has beta-1,3 glucanase activity and the heterogeneous glycosylation of the amino acid residues could be a source of the multiple allergenicity of natural Hev b 2. Previously we demonstrated that the recombinant form of Hev b 2 produced in Escherichia coli was not able to bind specific IgE, implying that the glycan chains seem to be important for the IgE reactivity. However, the IgE reactivity of the glycosylated latex allergens seems not to be restricted only to their glycan chains. Furthermore, our data have also demonstrated that in only a minority of patients with clinically relevant latex allergy were cross-reactive carbohydrate determinants (CCDs) recognised. In the case of these glycosylated allergens a combined binding is conceivable, comprising a peptide and a carbohydrate epitope on the same allergen molecule. In contrast to our patients with clear latex-induced latex sensitisation, in patients who are not de novo sensitised to the allergen tested, the carbohydrate epitopes recognised by the patients’ IgE are highly cross-reactive, and the clinical relevance of the positive test results have to be considered. Proteins with CCDs such as horseradish peroxidase (HRP) and bromelain could be used as an in vitro screening tool for differentiating true latex allergy from clinically insignificant elevated IgE to NRL. Based on the analysis of the sensitisation profiles, Hev b 2, 5, 6.01 and 13 are major allergens for HCW and SB patients and together with Hev b 1, the major allergen for SB, this allergen panel should be included in sufficient amounts in a standardised latex diagnostic extract. Furthermore, allergens such as Hev b 7, 8, 9, 10, 11 and 12 have to be considered for testing crossreactivity in individual cases. CCDs are only of minor relevance in patients with clinically relevant latex allergy. Component-resolved diagnostics for latex allergy have set the stage for specific immunotherapy strategies. Cross-reactivity between latex and fruits Several types of proteins have been identified as being involved in the latex-fruit syndrome: class I chitinases from avocado and banana containing an N-terminal hevein-like domain cross-react with hevein (Hev b 6.02), a major IgE allergen for patients allergic to NRL. Other important NRL-allergens are Hev b 2 (which shows cross-reactivity with proteins of bell pepper), Hev b 7, a patatin-like protein (cross-reactivity with its homologous protein in potato) and the Hev b 12 (lipid transfer protein showing cross-reactivity with its counterpart in peach). Furthermore, patients with allergy to plant-derived foods and associated pollinosis show a high frequency of IgE reactivity to the pan-allergen profilin (Hev b 8 in NRL), which may cause elevated serum IgE determination to NRL. Allergens like the enolase Hev b 9 and the manganese superoxide dismutase Hev b 10 may be the reason for cross-reactivity between moulds and latex. On the other hand, allergens like Hev b 1 and Hev b 3 are typical for latex; they do not show any cross-reactivity with other plants and therefore they are specific (Fig. 1). By using recombinant and native single allergens to determine individual NRL-sensitisation patterns, it is feasible to analyse the possible cross-reactivity or cosensitisation between different fruits and NRL. Concerning specific IgE reactivity to chestnut and NRL, with this approach we were able to detect that in patients’ sera recognising rHev b 5 and/or rHev b 6.01 the concomitant sensitisation to chestnut seemed to be independent of NRL. In contrast, patients’ sera with IgE predominantly reactive to rHev b 8 displayed crossinhibition between chestnut and NRL, indicating that Hev b 8 could be involved in the cross-reactivity between chestnut and NRL. By means of inhibition experiments we detected that Hev b 6.01/Hev b 6.02 were the relevant allergens for the cross-reactivity between NRL and acerola (Malpighia glabra L., Barbados cherry) in a patient with severe anaphylactic symptoms after consuming apple-juice containing traces of acerola. Knowing the responsible latex allergens which can elucidate more or less severe allergic reactions after ingestion of special fruits will make it possible to protect latex-sensitised patients from these effects.