|rHev b 8 is a CCD-free recombinant protein
Hev b 8 (13,56-58,60) is a profilin. Plant profilins are important panallergens. They are responsible for a significant percentage of pollen-related allergies. The observed frequencies of Hev b 8-specific IgE antibodies in sera of Latex-allergic patients in different risk groups range between 6 and 24% (1,57-58,60).
rHev b 8 has a sequence identity of 75% with Birch profilin (Bet v 2) (57). Recombinant isoforms of Hev b 8 with marginal differences in the amino acid sequence were reported to have no influence on the IgE-binding properties of the rHev b 8 isoforms. In a study evaluating the prevalence of serum IgE antibodies to rHev b 8, among 17 SB patients, IgE antibodies to rHev b 8 were found in 2, and in 5 of 25 sera (20%) from HCW. Further studies demonstrated the presence of IgE-binding epitopes on the Hev b 8 molecule which did not cross-react with Birch profilin. The study concluded that Latex profilin represents a minor allergen in Natural rubber latex (NRL) and may have IgE-binding epitopes different from Bet v 2 (58).
These factors may explain the variability in the prevalence of allergen-specific IgE binding to Latex profilin in studies. For example, skin tests and allergen-specific IgE antibodies to natural and recombinant purified Hev b 8 were positive in 15 of 17 spina bifida (SB) children and all 14 adults allergic to Latex. However, only 42% of the Latex-allergic patients had allergen-specific IgE levels of 0.35 kUA/L or higher, and only 39% of them exhibited IgE binding with any natural or recombinant Hev b 8 forms (56).
Between 30% and 50% of individuals who are allergic to Latex products are also allergic to specific plant foods, and this is aptly described as Latex-fruit syndrome. However, the roles of the Latex chitinase, Latex profilin and Latex beta-1,3-glucanase need to be clarified. This is well illustrated in a study, which reviewed simultaneous sensitisation to Latex and Bell pepper, sensitisation that had previously been reported. In sera of 4 patients with allergy to Latex and Bell pepper, 3 were shown to have IgE antibodies to profilin from Bell pepper and Latex. Two patients also had IgE antibodies to Hev b 2 (a beta-1,3-glucanase) and a homologous protein in Bell pepper. One patient was shown to have allergen-specific IgE to an L-ascorbate peroxidase, and another patient to a 38 kDa protein. The study concluded that Hev b 2 (beta-1,3-glucanase) and the Bell pepper L-ascorbate peroxidase were also cross-reactive allergens, and that profilin was responsible for some of the IgE cross-reactivity (59).
Similarly, other studies have demonstrated the variable responsibility of profilin in cross-reactivity between Latex profilin and other plant profilins. In a study of sera of 36 individuals containing IgE antibodies to Ragweed profilin, 35 reacted with profilin from Latex, indicating structural homologies between profilins from Latex and Ragweed. Fifty-nine percent of these sera were found to be positive for Latex-specific IgE. As profilin is also present in Banana, it was proposed that Latex profilin would likely be involved in cross-reactivity between Banana and Latex. However, among 19 individuals allergic to Latex, only 2 had anti-profilin IgE antibodies. The authors suggested that IgE antibodies to Latex profilin might be a questionable factor in sensitisation of occupationally exposed patients, but that sensitisation to profilin should be taken into account when interpreting the results of Latex-specific IgE investigation (60).
Recombinant profilin from Banana and Pineapple has a high sequence identity (71-84%) to known allergenic pollen and food profilin. In a study demonstrating IgE binding in sera to recombinant profilin, in 7/16 (44%) subjects with suspected Banana allergy, and in 8/19 (42%) subjects with suspected Pineapple allergy, high cross-reactivity to Birch pollen profilin Bet v 2 and Latex profilin Hev b 8 was demonstrated. Profilin was therefore shown to be an important mediator of IgE cross-reactivity between pollen and exotic fruits (61-62).
In a study using rHev b 8 to screen sera from Latex-allergic HCW with well-documented histories of food and pollen allergy and Latex-allergic SB patients, 12 of the 50 HCW and 2 of the 34 SB patients were sensitised to Hev b 8. All Hev b 8-sensitised patients showed allergic symptoms to pollen or plant foods. Cross-reactivity among profilins of Latex, pollen and plant food was demonstrated by their ability to inhibit IgE binding to rHev b 8. The authors concluded that primary sensitisation to Latex profilin in the majority of cases took place via pollen or food profilin, and that pollen- and food-allergic patients with profilin-specific IgE antibodies could be at risk of developing Latex allergy (57).
Other studies have also demonstrated the relevance of Latex profilin cross-reactivity, for example between Chenopodium profilin and Latex (65), and between 2 Rice profilin cDNAs (highly homologous to each other) and profilin from Maize, Bermuda grass, Timothy grass and Latex (63).