Identification, Cloning, and Sequence of a Major Allergen (Hev b 5) from Natural Rubber Latex (Hevea brasiliensis)

Abstract

Natural rubber latex in medical devices and consumer products has been implicated in over 1100 anaphylactic reactions that resulted in at least 15 deaths between 1988 and 1992 (1, 2). These reactions are caused by proteins that elute from the surfaces of certain latex products, especially gloves, barium enema catheters, balloons, and condoms. The proteins bind to antigen-specific IgE on tissue mast cells and trigger an anaphylactic response. While the production of IgE to latex proteins can occur in any individual, some individuals with uniquely high exposure to latex products appear to be at significantly greater risk for the production of these antibodies than the general population. These include health care workers and children with spina bifida (3-5). Interestingly, there appears to be significant clinical and immunochemical cross-reactivity between some latex proteins and allergens in certain fruits and vegetables, such as banana, kiwi, avocado, and potato, and patients with fruit and vegetable allergy may be at increased risk for reacting to latex proteins (6 -10).Latex allergy can be a devastating disease, with serious and occasionally fatal outcomes. The only treatment is avoidance (11,12), and health care workers with severe latex allergy may be required to change careers or leave health care entirely to avoid potentially dangerous exposure. Since anaphylactic episodes have occurred following skin testing with crude latex extracts (13-16), immunotherapy is not possible with currently available crude preparations. The identification and isolation of pure antigens, and the analysis of the B-and T-cell epitopes of these antigens, will facilitate the design and testing of safer regimens of immunotherapy.The proteins in natural rubber latex are derived from the commercial rubber tree, Hevea brasiliensis. Latex is produced in laticifers, which are specialized structures that consist of anastamosed latex-producing cells. Harvested Hevea latex is a complete cytosol with a high protein content (17, 18). Hevea latex is typically ammoniated when tapped to prevent premature coagulation and bacterial growth. Ammoniated latex is the source material for most of the products that elicit allergic reactions; thus, it clearly contains immunogenic material. However, immunochemical studies with ammoniated latex have failed to reveal the wealth of IgE-binding proteins found in non-ammoniated latex (NAL) 1 (19), which is collected into a liquid nitrogen-cooled container.From the first observations that products made from Hevea latex can elicit catastrophic allergic reactions in susceptible individuals, the component allergens have eluded conclusive identification. In part, this has been due to the complexity and instability of the proteins of Hevea latex. In addition, many investigators have been unable to obtain quantities of fresh material for examination and have been limited to the use of finished products or ammoniated latex (19) for their studies. In spite of these difficulties, several potential allergens have been i...

Isolation, Characterization, and Functional Analysis of a Novel cDNA Clone Encoding a Small Rubber Particle Protein from Hevea brasiliensis

“…Arokiaraj et al (6) observed that the GUS reporter gene introduced by Agrobacterium-mediated transformation was expressed in the latex of the transgenic Hevea plant. Genes expressed in the latex of Hevea can be divided into three groups based on the proteins they encode: 1) defense-related proteins such as hevein (7), chitinase (8), ␤-1,3-glucanase (9), and HEVER (10); 2) rubber biosynthesis-related proteins such as REF (4), hydroxymethylglutaryl-CoA reductase (11), and farnesyl diphosphate synthase (12); and 3) latex allergens (proteins) such as Hev b 3 (13), Hev b 4, Hev b 5 (14,15), and Hev b 7 (16). Biological functions of the allergenic proteins are largely unknown.…”

Identification and Characterization of Cross-Reactive Natural Rubber Latex and <i>Ficus benjamina </i>Allergens

“…With 2 exceptions, all subjects also had specific serum IgE antibodies to latex, as determined by the Pharmacia CAP system (Pharmacia &Upjohn Diagnostics, Uppsala, Sweden). The 2 subjects without detectable IgE to latex in the CAP system were confirmed to have latex allergy as they had elevated IgE to rHev b 5, a major latex allergen identified by Slater et al [8]. …”

Natural Rubber Latex Allergy

“…The WHO_International Union of Immunological Societies Allergen Nomenclature Committee (www.allergens.org) listed 14 NRL Hev b allergens (Hev b 1-14) characterized at the molecular level. It has included Hev b 1, rubber elongation factor (Chen et al, 1997); Hev b 2, b-1,3-glucanase (Yagami et al, 2002); Hev b 3, small rubber particle protein -a 24-kDa protein (Wagner et al, 1999); Hev b 4, a component of the microhelix protein complexlecithinase homologue; Hev b 6, prohevein/hevein precursor; Hev b 7; patatin-like protein; and Hev b 13, esterase (Beirnstein et al, 2003); Hev b 5, acidic protein -proline-rich protein (Slater et al, 1996); Hev b 8, profiling (Nieto et al, 2002); Hev b 9, enolase (Wagner et al, 2000); Hev b 10, manganese superoxide dismutase (Rihs et al, 2001); Hev b 12, non-specific lipid transfer protein 1 (Beezhold et al, 2003); and Hev b 11, class I chitinase, and Hev b 14, hevamine, that no allergenicity has been described yet. The epitopes identified as IgEbinding areas have been defined (Pedraza-Escalona et al, 2009;Rougé et al, 2010).…”