k215 Hev b 1

Summary

Hev b 1 is an allergen from natural rubber latex (NRL). It is a major allergen in people allergic to NRL as a result of repeated intraoperative contact, but not in those with occupational exposure or latex-fruit syndromes. Hev b 1 is a non-glycosylated protein from H. brasiliensis laticifers, belonging to the rubber elongation factor (REF) family. Following latex sap collection, treatment with ammonia and ultracentrifugation, Hev b 1 is found in the rubber phase, in association with the rubber latex particles. 

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 1 is a major allergen in latex-allergic patients with a history of multiple surgeries, especially those with a condition called spina bifida (SB), a defect of neural tube closure requiring repeated surgical interventions, long-term catheters and overall frequent and prolonged mucosal contact with medical devices (3, 4). The prevalence of Hev b 1 sensitization in SB patients may reach 81% (3, 5). Conversely, Hev b 1 is a minor allergen in latex-allergic patients with occupational exposure, such as healthcare workers (HCW), with a prevalence of 20% or less (3). Local exceptions are possible, such as in HCW from Taiwan, where Hev b 1 is a major allergen with a reported prevalence of 85% (6).

In an unselected population of 23,077 consecutive Italian subjects with a suspicion of airborne or food allergy, the prevalence of IgE sensitization to Hev b 1 was 0.34%, ranking 68th out of 75 assayed allergenic molecules (7). Apparent monosensitization to Hev b 1 was initially reported in 45% of SB patients (8), but later reports found lower prevalence figures, e.g. in 3 out of 31 (9.6%) SB patients (5) and in 4 out of 56 (7.1%) subjects with a suspicion of allergy (7). Hev b 1 sensitization in SB patients was reported in both latex-allergic patients and in those who had not experienced latex allergy (5).

Environmental Characteristics

Source and tissue

Hev b 1 belongs to the REF family (9, 10). In intact laticifer cells, Hev b 1 is a component of membrane protein-lipid rafts (11); after collection of the latex sap, ammonia treatment and ultracentrifugation, Hev b 1 is found as an insoluble allergen of the rubber phase, in association with rubber particles (3)

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 spina bifida patients) and latex allergy in the context of pollen and/or plant food allergy (3). 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, due to appropriate prevention and diagnosis, including the assessment of Hev b 1 sensitization in the diagnostic algorithm (3, 13, 14).

As explained above, Hev b 1 sensitization is predominantly found in SB and /or multiple surgery patients; however, this sensitization may occur at similar frequency in both latex-allergic and in asymptomatic SB and MS patients (5). In contrast, other latex molecular allergens are better discriminants of latex allergy vs asymptomatic latex sensitization. As a result, a panel of major allergens comprising Hev b 1 alongside Hev b 5, Hev b 6, and Hev b 3 is advised in order to identify clinically relevant NRL sensitization (3). Once the clinical relevance is established, Hev b 1 sensitization in the context of a medical history of SB and/or multiple surgery allows the identification of mucosal contact-related latex allergy and the implementation of patient care guidelines including latex avoidance (3, 13, 14).

Clinical relevance in occupational latex allergy 

This type of latex allergy occurs in people who are occupationally exposed to NRL, such as HCW, and has also experienced a sharp decrease since the 1990s (3, 14). Hev b 1 is a minor allergen in this context, with Hev b 1 sensitization demonstrated in 11 to 22% of HCW (5, 15, 16). Indeed, Hev b 1 is an insoluble protein bound to rubber particles in latex devices, and therefore will not become aerosolized (3, 5). Geographic variations are possible, such as reported in Taiwan HCW with a prevalence of Hev b 1 sensitization up to 85% (6). Hev b 1 assessment as part of the latex sensitization pattern contributes to stratification and prevention strategies (4).

Clinical relevance in pollen and/or plant food allergy

Hev b 1 sensitization is uncommon in patients with pollen and/or plant food allergy who are sensitized to NRL extracts, but has been reported in patients experiencing both latex glove anaphylaxis and allergy to fruit (14, 17).

Disease severity and prediction

In patients sensitized to NRL extract, the demonstration of Hev b 1 sensitization is considered as a marker of high risk of perioperative latex allergy (13)

Cross-reactive molecules

Hev b 1 shares 72% sequence similarity with Hev b 3, another member of the REF family (18).

Molecular Aspects

Biochemistry

Hev b 1 is a protein with a molecular weight of 14 kDa, making up 10 to 60% of the total protein content of latex sap (15), able to form a noncovalent homotetramer (19).

Isoforms, epitopes, antibodies

As of October 9th, 2021, Hev b 1 possesses a single isoallergen officially published by the World Health Organization (WHO) and the International Union of Immunological Societies (IUIS) Allergen Nomenclature (9).

Cross-reactivity due to structural similarity

Hev b 1 displays sequence identity limited to REF family, including REF and small rubber particle protein (SRPP) homologs (11). Structural similarity resulting in reciprocal inhibition has been demonstrated between Hev b 1 and Hev b 3 (18, 20).

Diagnostic Relevance

Disease Severity

In the diagnostic context of latex allergy, sensitization to Hev b 1 is considered as a marker of high risk of perioperative anaphylaxis (3, 13, 14).

Cross-Reactivity

Hev b 1 cross-reactivity outside NRL has not been described (14). 

Exposure

Hev b 1 sensitization is believed to occur during repeated mucosal contact with latex-containing medical devices, preferentially during repeated perioperative exposure, as seen in SB patients (3). As a rubber particle protein, Hev b 1 is insoluble and does not become aerosolized except for powdered gloves, making respiratory exposure unlikely (3, 15).

Compiled By

Author: Joana Vitte

Reviewer: Dr. Christian Fischer

Last reviewed: November  2021