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. South-East Asia is currently the largest producer of NRL worldwide.
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. The prevalence of Hev b 1 sensitization in SB patients may reach 81%. 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. Local exceptions are possible, such as in HCW from Taiwan, where Hev b 1 is a major allergen with a reported prevalence of 85%.
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. Apparent monosensitization to Hev b 1 was initially reported in 45% of SB patients, but later reports found lower prevalence figures, e.g. in 3 out of 31 (9.6%) SB patients and in 4 out of 56 (7.1%) subjects with a suspicion of allergy. Hev b 1 sensitization in SB patients was reported in both latex-allergic patients and in those who had not experienced latex allergy.
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. 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, due to appropriate prevention and diagnosis, including the assessment of Hev b 1 sensitization in the diagnostic algorithm.
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. 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. 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.
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. Hev b 1 is a minor allergen in this context, with Hev b 1 sensitization demonstrated in 11 to 22% of HCW. Indeed, Hev b 1 is an insoluble protein bound to rubber particles in latex devices, and therefore will not become aerosolized. Geographic variations are possible, such as reported in Taiwan HCW with a prevalence of Hev b 1 sensitization up to 85%. Hev b 1 assessment as part of the latex sensitization pattern contributes to stratification and prevention strategies.
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.
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
Cross-reactive molecules
Hev b 1 shares 72% sequence similarity with Hev b 3, another member of the REF family.
Diagnostics
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.
Cross-Reactivity
Hev b 1 cross-reactivity outside NRL has not been described.
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. As a rubber particle protein, Hev b 1 is insoluble and does not become aerosolized except for powdered gloves, making respiratory exposure unlikely.
References
- Grogan K, Pflugmacher D, Hostert P, Mertz O, Fensholt R. Unravelling the link between global rubber price and tropical deforestation in Cambodia. Nat Plants. 2019;5(1):47-53.
- Warren-Thomas E, Dolman PM, Edwards DP. Increasing Demand for Natural Rubber Necessitates a Robust Sustainability Initiative to Mitigate Impacts on Tropical Biodiversity. Conservation Letters. 2015;8(4):230-41.
- M R. Latex allergy. Pediatr Allergy Immunol. 2016(27):165-70.
- Steering Committee A, Review Panel M. A WAO - ARIA - GA(2)LEN consensus document on molecular-based allergy diagnosis (PAMD@): Update 2020. World Allergy Organ J. 2020;13(2):100091.
- Raulf-Heimsoth M, Rihs HP, Rozynek P, Cremer R, Gaspar A, Pires G, et al. Quantitative analysis of immunoglobulin E reactivity profiles in patients allergic or sensitized to natural rubber latex (Hevea brasiliensis). Clin Exp Allergy. 2007;37(11):1657-67.
- Lee MF, Chen YH, Lin HC, Wang HL, Hwang GY, Wu CH. Identification of hevamine and hev B 1 as major latex allergens in Taiwan. Int Arch Allergy Immunol. 2006;139(1):38-44.
- Scala E, Alessandri C, Bernardi ML, Ferrara R, Palazzo P, Pomponi D, et al. Cross-sectional survey on immunoglobulin E reactivity in 23,077 subjects using an allergenic molecule-based microarray detection system. Clin Exp Allergy. 2010;40(6):911-21.
- Chen Z, Cremer R, Posch A, Raulf-Heimsoth M, Rihs HP, Baur X. On the allergenicity of Hev b 1 among health care workers and patients with spina bifida allergic to natural rubber latex. The Journal of allergy and clinical immunology. 1997;100(5):684-93.
- http://www.allergen.org. http://www.allergen.org 2021 [September 23rd, 2021].
- http://www.meduniwien.ac.at/allfam/. AllFam 2021 [October 9, 2021].
- http://www.uniprot.org/uniprot/P15252. UniProt 2021 [October 9, 2021].
- Niggemann B, Breiteneder H. Latex allergy in children. Int Arch Allergy Immunol. 2000;121(2):98-107.
- Cardona V, Ansotegui IJ. Component-resolved diagnosis in anaphylaxis. Curr Opin Allergy Clin Immunol. 2016;16(3):244-9.
- Ebo DG, Bridts CH, Rihs HP. Hevea latex-associated allergies: piecing together the puzzle of the latex IgE reactivity profile. Expert Rev Mol Diagn. 2020;20(4):367-73.
- Rihs HP CZ, Schumacher S, Rozynek P, Cremer R, Lundberg M et al. Recombinant Hev b 1: large-scale production and immunological characterization. Clin Exp Allergy 2000(30):1285-92.
- Vandenplas O, Froidure A, Meurer U, Rihs HP, Rifflart C, Soetaert S, et al. The role of allergen components for the diagnosis of latex-induced occupational asthma. Allergy. 2016;71(6):840-9.
- Sompornrattanaphan M, Kreetapirom P, Srinoulprasert Y, Kanistanon D, Klinniyom A, Wongsa C, et al. Severe anaphylaxis after pelvic examination: a case report of dual latex and chlorhexidine allergies. Allergy Asthma Clin Immunol. 2019;15:19.
- Wagner B, Krebitz M, Buck D, Niggemann B, Yeang HY, Han KH, et al. Cloning, expression, and characterization of recombinant Hev b 3, a Hevea brasiliensis protein associated with latex allergy in patients with spina bifida. The Journal of allergy and clinical immunology. 1999;104(5):1084-92.
- Czuppon AB, Chen Z, Rennert S, Engelke T, Meyer HE, Heber M, et al. The rubber elongation factor of rubber trees (Hevea brasiliensis) is the major allergen in latex. The Journal of allergy and clinical immunology. 1993;92(5):690-7.
- Banerjee B, Kanitpong K, Fink JN, Zussman M, Sussman GL, Kelly KJ, et al. Unique and shared IgE epitopes of Hev b 1 and Hev b 3 in latex allergy. Molecular immunology. 2000;37(12-13):789-98.