Source material: A native extract of allergen Ole e 9 purified from a natural Olea europaea pollen.
Common names: 1,3-beta-glucanase.
Biological function: A glucanase.
Mw: 46.4 kDa.
Olea europaea, the Olive tree, is one of the most important causes of seasonal respiratory allergy in some regions of southern Europe, particularly the Mediterranean area (21, 29, 30), and also in other parts of the world where this tree is now grown. The Olive tree is a member of the Oleaceae family, which has 4 important genera: Olive (Olea), Ash (Fraxinus), Lilac (Syringa), and Privet (Ligustrum).
The Olive tree probably originated in Asia Minor, spread to the Mediterranean region, and was then introduced into North America (especially California and Arizona), South America (Chile), Australia and South Africa. Although Olive trees in North America are found only in the Southwest, Ash and Privet are widespread, a circumstance of relevance to cross-reactivity (31). Countries and regions have distinct varieties of Olive
Olive pollens can induce asthma, allergic rhinitis and allergic conjunctivitis in sensitised individuals. The majority of studies demonstrate a higher prevalence of rhinoconjunctivitis than of asthma (29).
Ole e 9 is a 1,3-β-glucanase composed of 2 structurally and immunologically well-defined domains (1). The N-terminal domain is involved in IgG and IgE cross-reactivity with other pollens, plant-derived foods, and Latex (2), and the C-terminal domain is a glucan-binding module whose sequence is similar to that of Ole e 10 (3, 4). Ole e 10 is a protein that interacts with 1,3-β-glucan, and the first reported member of a novel family of β-glucan-binding modules (5).
Ole e 9 has been shown to have at least two active IgE-binding epitopes (domains): the N-terminal domain (rNtD) and C-terminal domain (rCtD). These different domains appear to result in different disease expression in at least 2 subsets of patients with Olive pollen allergies (6): those at risk of cross-reactivity between Olive pollen, Latex, fruit, and vegetables (rNtD), and patients who could develop asthma due to sensitisation to rCtD, as this domain shows homology (53% identity) and high cross-reactivity with Ole e 10, which has been associated with more severe bronchial asthma in Olive-allergic patients  (7).
To elaborate: Sensitivity to Ole e 9 has been associated with the severity of allergic rhinitis and asthma (8). Furthermore, sensitivity to Ole e 10 has also been associated with severity and persistence of asthma (7), and as Ole e 10 and the C-terminal domain of Ole e 9 are homologous polypeptides, it has been suggested that the correlation between Ole e 10 and asthma symptoms could be extended to sensitivity to the C-terminal domain of Ole e 9 (9).
Ole e 9 in particular has a low presence, except in areas of high-exposure to Olive trees (8, 10). Studies have shown that the allergen profiles of Olive-allergic patients from areas with a high pollen count (such as Jaén in Andalusia, southern Spain) are notably different from those in areas with a low count (e.g. Madrid, central Spain) (11). Sensitisation to Ole e 7 and Ole e 9 were lower (14.4% and 10.7%, respectively) in geographic areas where Olive pollen exposure was low, and higher (over 35%) in areas of intense Olive tree cultivation (12). In areas where intense Olive tree cultivation occurred, the highest frequency of allergenicity was found to be to Ole e 6 (13), Ole e 7 (14), Ole e 9 (1), and Ole e 10 (5, 10). It has been reported that the major allergens identified (with more than 50% frequency) in individuals with marked allergic rhinitis and asthma were Ole e 1, Ole e 7, Ole e 9, and Ole e 10. However, heterogenous responses do occur; and although an IgE reactivity pattern involving more than 3 allergens was noted in around 75% of patients, 45 different IgE patterns were observed when 8 allergens were tested on a group of 156 patients (8).
Ole e 9 (and Ole e 10) has also been shown to be a relevant allergen in the pollen-Latex-fruit syndrome (also known as the Latex-fruit syndrome), a syndrome particularly involving the association between allergy to Latex and (most commonly) Kiwi, Banana, Chestnut, and Avocado (8, 15).
The N-terminal domain of Ole e 9 is similar to other 1,3-β-glucanases in other plants, including Hev b 2, the 1,3-β-glucanase in Latex (6). This panallergen may result in IgE cross-reactivity between Latex, vegetables (e.g., Tomato, Potato), fruits (e.g., Banana), and pollens that contain this protein (8, 11). However, the exact clinical relevance of these cross-reactive allergens needs to be fully evaluated (8). A study evaluating the use of recombinant N-terminal (rNtD) and C-terminal domains (rCtD) of Ole e 9 in 33 Ole e 9-allergic patients reported that out of a total of 33 patients, 94% (16) were reactive to rNtD or rCtD, 79% (17) to rNtD, 67% (18) to rCtD, and 52% (19) to both (6). Importantly, 27% (20) were reactive to rNtD alone and 15% (21) to rCtD alone, suggesting that many Ole e 9-allergic patients (42%) can be specifically sensitised to the N- or the C-terminal domains of the allergen (6), and therefore a positive Ole e 9 result needs to be interpreted with the clinical picture.
Other allergens present in Latex and with structural homology to Olive pollen allergens do occur: Hev b 8 (profilin) and Ole e 2; Hev b 10 (manganese superoxide dismutase) and Ole e 5 (22).
Ole e 7 and Ole e 9 may also assist in the assessment of immunotherapy in the Olive tree pollen-allergic individual. It has been reported that patients sensitised to Ole e 7 or Ole e 9 (but not to the pollen panallergens polcalcin or profilin) were less tolerant of immunotherapy (23, 24). Also, in areas of intense Olive tree cultivation, sensitisation to Ole e 7 (but not Ole e 9) was demonstrated to be independent of Ole e 1, with 40% of Ole e 1-negative patients being sensitised to Ole e 7 (25), suggesting a benefit of standardising allergen extracts for immunotherapy by assessing the content of relevant minor allergens (24).
Extreme allergenic differences between pollens obtained from different cultivars have been demonstrated, which is a recommendation for the use of native/recombinant allergens in epidemiological studies. The individual allergen content of five batches of Olive pollen collected in Spain from different Olive varieties reported Ole e 7 varying from 806 to 2335µg Ole e 7/g, and Ole e 9 from 1368 to 2044µg Ole e 9/g (26). This was attributed to the variability of the major IgE-binding component (27). The concentration of Ole e 9 has also been reported to vary several hundred times between different pollen batches (28). Furthermore, as Ole e 9 and Ole 10 occur in a low concentration in Olive tree pollen, the use of native or recombinant Ole e 9 (and 10) would therefore be beneficial (9).
- Huecas S, Villalba M, Rodriguez R. Ole e 9, a major olive pollen allergen is a 1,3-beta-glucanase. Isolation, characterization, amino acid sequence, and tissue specificity. J Biol Chem 2001;276(30):27959-66.
- Palomares O, Villalba M, Quiralte J, Polo F, Rodriguez R. 1,3-beta-glucanases as candidates in latex-pollen-vegetable food cross-reactivity. Clin Exp Allergy 2005;35(3):345-51.
- Palomares O, Villalba M, Rodriguez R. The C-terminal segment of the 1,3-beta-glucanase Ole e 9 from olive (Olea europaea) pollen is an independent domain with allergenic activity: expression in Pichia pastoris and characterization. Biochem J 2003;369(Pt 3):593-601.
- Rodriguez R, Villalba M, Batanero E, Palomares O, Salamanca G. Emerging pollen allergens. Biomed Pharmacother 2007;61(1):1-7.
- Barral P, Batanero E, Palomares O, Quiralte J, Villalba M, Rodriguez R. A major allergen from pollen defines a novel family of plant proteins and shows intra- and interspecies [correction of interspecie] cross-reactivity. J Immunol 2004;172(6):3644-51.
- Barber D, Carpizo J, Garcia-Rumbao MC, Polo F, Juan F. Allergenic variability in olea pollen. Ann Allergy 1990 Jan;64(1):43-6.
- Quiralte J, Llanes E, Barral P, Arias de Saavedra JM, Saenz de San Pedro B, Villalba M, Florido JF, Rodriguez R, Lahoz C, Cardaba B. Ole e 2 and Ole e 10: new clinical aspects and genetic restrictions in olive pollen allergy. Allergy 2005;60(3):360-5.
- Quiralte J, Palacios L, Rodríguez R, Cárdaba B, Arias de Saavedra JM, Villalba M, Florido JF, Lahoz C. Modelling diseases: the allergens of Olea europaea pollen. J Investig Allergol Clin Immunol 2007;17 Suppl 1:24-30.
- Rodríguez R, Villalba M, Batanero E, Palomares O, Quiralte J, Salamanca G, Sirvent S, Castro L, Prado N. Olive pollen recombinant allergens: value in diagnosis and immunotherapy. J Investig Allergol Clin Immunol 2007;17 Suppl 1:4-10.
- Moreno-Aguilar C. Improving pollen immunotherapy: minor allergens and panallergens. Allergol Immunopathol (Madr) 2008;36(1):26-30.
- Gonzalez EM, Villalba M, Rodriguez R. Allergenic cross-reactivity of olive pollen. Allergy 2000;55(7):658-63.
- Barber D, de la Torre F, Feo F, Florido F, Guardia P, Moreno C, Quiralte J, Lombardero M, Villalba M, Salcedo G, Rodríguez R. Understanding patient sensitization profiles in complex pollen areas: a molecular epidemiological study. Allergy 2008;63(11):1550-8.
- Batanero E, Ledesma A, Villalba M, Rodriguez R. Purification, amino acid sequence and immunological characterization of Ole e 6, a cysteine-enriched allergen from olive tree pollen. FEBS Lett 1997;410:293-6.
- Tejera ML, Villalba M, Batanero E, Rodriguez R. Identification, isolation, and characterization of Ole e 7, a new allergen of olive tree pollen. J Allergy Clin Immunol 1999;104(4 Pt 1):797-802.
- Blanco C, Carrillo T, Castillo R, Quiralte J, Cuevas M. Latex allergy: clinical features and cross-reactivity with fruits. Ann Allergy 1994;73(4):309-14.
- Caballero T, Romualdo L, Crespo JF, Pascual C, Munoz-Pereira M, et al. Cupressaceae pollinosis in the Madrid area. Clin Exp Allergy 1996;26(2):197-201.
- Tamir R, Pick AI, Topilsky M, Kivity S. Olive pollen induces asthmatic response. Clin Exp Allergy 1991;21(3):329-32.
- Corsico R, Falagiani P, Ariano R, Berra D, Biale C, Bonifazi F, Campi P, et al. An epidemiological survey on the allergological importance of some emerging pollens in Italy. J Investig Allergol Clin Immunol 2000;10(3):155-61.
- D'Amato G, Liccardi G. Pollen-related allergy in the European Mediterranean area. Clin Exp Allergy 1994;24(3):210-9.
- Soriano JB, Anto JM, Sunyer J, Tobias A, Kogevinas M, Almar E, et al. Risk of asthma in the general Spanish population attributable to specific immunoresponse. Spanish Group of the European Community Respiratory Health Survey. Int J Epidemiol 1999;28(4):728-34.
- D'Amato G, Liccardi G. The increasing trend of seasonal respiratory allergy in urban areas. Allergy 2002;57 Suppl 71:35-6.
- Palomares O, Villalba M, Quiralte J, Rodriguez R. Allergenic contribution of the IgE-reactive domains of the 1,3-beta-glucanase Ole e 9: diagnostic value in olive pollen allergy. Ann Allergy Asthma Immunol 2006;97(1):61-5.
- Serrano Delgado P. Sensibilización a alérgenos minoritarios de Olea europaea como causa de reacciones sistémicas por inmunoterapia alérgenoespecífica. [Doctoral thesis] Cordoba (Spain): University of Cordoba, 2007.
- Cited in: Barber D, de la Torre F, Feo F, Florido F, Guardia P, Moreno C, Quiralte J, Lombardero M, Villalba M, Salcedo G, Rodríguez R. Understanding patient sensitization profiles in complex pollen areas: a molecular epidemiological study. Allergy 2008;63(11):1550-8.
- Barber D, De la Torre F, Feo F, Florido F, Guardia P, Moreno C, Quiralte J, Lombardero M, Villalba M, Salcedo G, Rodriguez R (EXPO Study): Allergen profile of pollen allergic patients from an olive-rich area. Unpublished.
- Barber D, Moreno C, Ledesma A, Serrano P, Galán A, Villalba M, Guerra F, Lombardero M, Rodríguez R. Degree of olive pollen exposure and sensitization patterns. Clinical implications. J Investig Allergol Clin Immunol 2007;17 Suppl 1:11-6.
- Barber D, Polo F, Lombardero M, Villalba M, Rodríguez R. The importance of minor allergens in allergen standardization. Arb Paul Ehrlich Inst Bundesamt Sera Impfstoffe Frankf A M. 2006;(95):128-34; discussion 134, 155.
- Duffort O, Palomares O, Lombardero M, Villalba M, Barber D, Rodriguez R, Polo F. Variability of Ole e 9 allergen in olive pollen extracts: Relevance of minor allergens in immunotherapy treatments. Int Arch Allergy Immunol 2006;140(2):131-8.
- Liccardi G, D'Amato M, D'Amato G. Oleaceae pollinosis: a review. Int Arch Allergy Immunol 1996;111(3):210-7.
- Florido López JF. Symposium Internacional ‘Alergia a Polen de Olivo’. Aspectos clínicoepidemiológicos. Rev Esp Allergol Inmunol Clin 1994;9(2):1-31.
- Kernerman SM, McCullough J, Green J, Ownby DR. Evidence of cross-reactivity between olive, ash, privet, and Russian olive tree pollen allergens. Ann Allergy 1992;69(6):493-6.