Hev b 6.02, Latex
Summary
Hev b 6.02, also called hevein, is a major allergen from natural rubber latex (NRL) of particular importance in occupational latex allergy and latex-food syndrome (LFS). Hev b 6.02, naturally found in H. brasiliensis laticifers, locates to the B-serum phase of NRL after collection, treatment with ammonia and ultracentrifugation of the latex sap. Hev b 6.02 is the post-translational N-terminal mature form of prohevein (Hev b 6.01) and comprises most of its IgE-binding epitopes. Hev b 6.02 is a non-glycosylated, disulfide-bond stabilized lectin involved in antimicrobial plant defense thanks to its chitinase and ribonuclease activity.
Epidemiology
Worldwide distribution
NRL is extracted from rubber trees. Hevea brasiliensis, native to the Amazon rainforest, is more productive than other species of rubber trees and has therefore been imported to other continents. South-East Asia is currently the largest producer of NRL worldwide.
Hev b 6.02 is a major allergen in all categories of latex-allergic patients, i.e., occupational allergy, LFS, and to a lesser extent in those with a history of multiple surgical interventions. The prevalence of Hev b 6.02 sensitization in latex-allergic patients may reach 78% in healthcare workers (HCW) and 58% in those with a history of multiple surgery. Conversely, the prevalence of Hev b 6.02 sensitization in spina bifida patients may be as low as 27%.
In an unselected population of 23,077 consecutive Italian subjects with a suspicion of airborne or food allergy, 1.3% displayed detectable IgE sensitization to Hev b 6 isoallergens, ranking 52 among 75 assayed allergenic molecules. In this study, Hev b 6 sensitization exhibited a statistically significant gender bias (women: 1.61% vs men 0.91%, p<0.001). Hev b 6.02 sensitization may be demonstrated in latex-sensitized, symptom-free patients, although with lower figures of prevalence and quantitative IgE levels.
Clinical Relevance
Detailed information regarding latex allergy is available in the whole allergen section. In brief, NRL is associated with occupational latex allergy (extended to latex allergy occurring in multiple surgery and SB patients) and latex allergy in the context of pollen and/or plant food allergy. The following sections apply to adult and pediatric subjects alike.
Clinical relevance in latex allergy occurring in spina bifida and other patients undergoing multiple surgeries
The prevalence of this type of latex allergy has diminished since the 1990s in countries where appropriate prevention and diagnosis have been implemented, including the assessment of Hev b 6.02 sensitization in the diagnostic algorithm. A panel of major allergens comprising Hev b 6.02 alongside Hev b 5, Hev b 1, and Hev b 3 is advised as markers of genuine latex allergy, in order to identify clinically relevant NRL sensitization.
Clinical relevance in occupational latex allergy
This type of latex allergy occurs in people who are occupationally exposed to NRL using and manufacturing, and has also experienced a sharp decrease since the 1990s in countries where prevention measures have been implemented. Hev b 6.02 is a major allergen in this context, with Hev b 6.02 sensitization demonstrated in up to 78% of HCW. Hev b 6.02 sensitization is associated to frequent contact with NRL gloves and presents mainly with muco-cutaneous (urticaria, angio-edema) and oculo-respiratory (asthma, rhinoconjunctivitis) symptoms. Indeed, Hev b 6.02 may become aerosolized from gloves, or act through direct contact. Hev b 6.02 assessment as part of the latex sensitization pattern contributes to stratification and prevention strategies
Clinical relevance in latex-food syndromes (LFS)
LFS comprises reactions to foods which occur in 21-58% of latex-allergic or latex-sensitized patients and have been attributed to cross-reactivity from latex allergens, although food-induced reactions may precede latex-associated ones. Such foods include the originally identified exotic fruit (banana, avocado) but have since extended to a large array of other plant foods. Hev b 6.02 is widely recognized as a major contributor to LFS. Hev b 6.02 sensitization is a frequent finding in patients with LFS who are sensitized to NRL extracts, and has been reported in patients experiencing both latex glove anaphylaxis and allergy to fruit.
At the molecular level, Hev b 6.02 supports cross-reactivity with hevein-like domains which are found in class I and IV chitinases, widely distributed plant defense enzymes. Mus a 2 from banana, Tri a 18 from wheat, Pers a 1 from avocado, are examples of IUIS/WHO validated food chitinases involved in LFS through cross-reactivity with Hev b 6.02.
Disease severity and prediction
In patients sensitized to NRL extract, the demonstration of sensitization to Hev b 6.02 (or to other Hev b 6 marker) is considered as a marker of genuine latex allergy.
Clinical manifestations of of Hev b 6.02-associated latex allergy include muco-cutaneous manifestations such as urticaria and angio-edema, asthma, rhinoconjunctivitis, and perioperative hypersensitivity.
Clinical relevance in occupational latex allergy
Cross-reactivity between NRL and Ficus benjamina has been reported, with 25% of latex-allergic HCW showing sensitization to F. benjamina and possible involvement of a hevein domain containing protein from F. benjamina, cross-reactive with Hev b 6.02. A significant association between NRL and F. benjamina association was confirmed in an independent prospective study, however, the figures were much lower, with 10.6% of F. benjamina-sensitized patients also sensitized to NRL, and just one out of 11 with fruit allergy and sensitization to both NRL and F. benjamina demonstrating involvement of hevein. These differences may be attributed to a different study design, i.e. screening consecutive subjects with potential inhalant allergy rather than focusing on confirmed latex-allergic HCW. To date, no hevein domain containing allergen from F. benjamina has been registered with the IUIS/WHO Allergen Nomenclature.
Cross-reactive molecules
Hev b 6.02 shares clinically significant sequence similarity and cross-reactivity with identified allergens containing hevein-like domains, mainly class I and class IV chitinases, explaining an extended range of plant food cross-reactivity.
Diagnostics
Disease Severity
In the diagnostic context of latex allergy, sensitization to Hev b 6.02 is considered as a marker of genuine latex allergy, high risk of perioperative anaphylaxis, and high risk of a positive specific inhalation challenge with latex.
Cross-Reactivity
Hev b 6.02 displays clinically relevant cross-reactivity with related allergens from latex (Hev b 11) and certain plant foods, based on the similarity of the hevein domain (.
Exposure
Hev b 6.02 sensitization is believed to occur mainly through contact or inhalation while using or manufacturing NRL-containing products. Hev b 6.02 may become aerosolized, resulting in respiratory exposure. Hev b 6.02 was still detectable in some but not all latex products investigated in a 2017 study, such as medical and household gloves, condoms, and toy balloon, supporting continued exposure avoidance for latex-allergic patients.
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