k224 Hev b 11

Summary

Hev b 11, a class I chitinase, is a minor allergen from natural rubber latex (NRL), associated to occupational latex allergy and latex-food syndrome (LFS). Hev b 11 is naturally found in H. brasiliensis laticifers (Hev b 11.0101) and leaves (Hev b 11.0102). Hev b 11 locates to the B-serum phase of NRL after collection, treatment with ammonia and ultracentrifugation of the latex sap. Hev b 11 is a non-glycosylated, disulfide-bond stabilized lectin comprising a hevein-like domain.

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 [1]. South-East Asia is currently the largest producer of NRL worldwide [2].

Hev b 11 is a minor allergen in all categories of latex-allergic patients, i.e., occupational allergy, LFS, and multiple surgical interventions with or without spina bifida (SB). The average prevalence of Hev b 11 sensitization in latex-allergic patients is 15 to 23% [3-5], with large variations from 0 to 50% ([6, 7]. Hev b 11 sensitization is usually associated to Hev b 6.02 sensitization ([6, 8].

In an unselected population of 23,077 consecutive Italian subjects with a suspicion of airborne or food allergy, 0.47% displayed detectable IgE sensitization to Hev b 11, ranking 62 among 75 assayed allergenic molecules [9]. In this study, Hev b 11 monosensitization was not observed.

Environmental Characteristics

Source and tissue

The two isoforms of Hev b 11 display different tissue locations in H. brasiliensis. Hev b 11.0101 is present in the lutoids of laticifer cells and hence in the latex sap collected from the trunk [5]. After collection of the latex sap, ammonia treatment and ultracentrifugation, Hev b 11.0101 is found mainly as a soluble allergen of the B-serum phase [5]. Hev b 11 is considered as an allergen of moderate abundance in NRL extracts [10]. Hev b 11.0102 is found in the leaves of H. brasiliensis [11].

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 [5]. The following sections apply to adult and pediatric subjects alike [12].

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. As a minor allergen, Hev b 11 testing is advised only as a third step in the diagnostic algorithm, following the assessment of major allergens (Hev b 1, Hev b 3, Hev b 5, Hev b 6.02) and panallergens (Hev b 8, carbohydrate determinants) panels [13].

Clinical relevance in occupational latex allergy

This type of latex allergy occurs in people who are occupationally exposed to NRL [5], and has also experienced a sharp decrease since the 1990s in countries where prevention measures have been implemented [13]. Hev b 11 is a minor allergen in this context too, and similarly to the above section, its assessment is a complement of testing for major allergens and panallergens [13].

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 [14]. 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 [15]. 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.

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 [16], although food-induced reactions may precede latex-associated ones [5]. Such foods include the originally identified exotic fruit (banana, avocado) but have since extended to a large array of other plant foods [16, 17]. Class I chitinases Hev b 11 and Hev b 6 are widely recognized as major contributors to LFS [5, 16]. Hev b 11 sensitization is often associated to Hev b 6 in patients with LFS who are sensitized to NRL extracts [7, 16], and has been reported in patients experiencing both latex glove anaphylaxis and allergy to fruit [18].

At the molecular level, Hev b 11 supports cross-reactivity with hevein-like domains which are found in class I and IV chitinases, widely distributed plant defense enzymes [17]. Mus a 2 from banana, Tri a 18 from wheat, Pers a 1 from avocado, are examples of IUIS/WHO registered food chitinases  involved in LFS through cross-reactivity with Hev b 11 [17, 19].

Disease severity and prediction

Among latex-sensitized patients, Hev b 11 sensitization is more prevalent in those experiencing surgery-related or occupational latex-induced symptoms as compared to those with asymptomatic latex sensitization [4, 6, 7], e.g.  24% vs 4%, p = 0.02 in occupational latex allergy [4].

Cross-reactive molecules

Hev b 11 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 [17, 20]. 

Molecular Aspects

Biochemistry

Hev b 11 is an acidic protein of 30 kDa containing a hevein-like domain stabilized by four disulfide bonds, which does not bear glycosylated groups, and is categorized as a lectin due to its ability to bind chitin, a complex sugar [17, 20, 21]

Isoforms, epitopes, antibodies

As of October 9th, 2021, Hev b 11 comprises two isoallergens officially published by the World Health Organization (WHO) and the International Union of Immunological Societies (IUIS) Allergen Nomenclature: Hev b 11.0101 from NRL and Hev b 11.0102 from H. brasiliensis leaves [19].

Cross-reactivity due to structural similarity

Cross-reactivity at the IgE binding level resulting in clinically relevant reactions has been reported for Hev b 11 and hevein domain-containing homologs from banana (Mus a 2), avocado (Pers a 1), chestnut (Cas s 5), wheat (Tri a 18), kiwi, and other plant food chitinases [8, 16, 17]. Hev b 11 displays structural similarity and cross-reactivity with Hev b 6, hevein, a major latex allergen [5, 17].

Diagnostic Relevance

Disease Severity

In the diagnostic context of latex allergy, sensitization to Hev b 11 is considered as a marker of LFS [5, 16], but has also been associated with a higher rate of a positive specific inhalation challenge with latex [4].

Cross-Reactivity

Hev b 11 displays clinically relevant cross-reactivity with related allergens from latex (Hev b 6) and certain plant foods, based on the similarity of the hevein domain ([16, 17].

Exposure

Hev b 11 sensitization is believed to occur mainly through contact or inhalation upon exposure to NRL-containing products [5].

Compiled By

Author: Joana Vitte

Reviewer: Dr. Christian Fischer

Last reviewed: November  2021