Source material: A native extract of allergen Ole e 7 purified from a natural Olea europaea pollen.
Common names: Lipid transfer protein, LTP.
Biological function: A lipid transfer protein.
Mw: 9.9-10.3 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 (2,23,24), 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 (25). 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 (23).
Ole e 7 is a lipid transfer protein which exhibits a high degree of polymorphism. Its molecular mass is in the range of 9.9 kDa to 10,3 kDa. Ole e 7 has an average frequency of about 47% in patients with Olive allergy (1).
Ole e 7 belongs to the nonspecific lipid transfer protein family, a family which (in vegetables and fruit) usually shows a high degree of cross-reactivity (e.g. Peach, Apple, Cherry, Apricot, Orange, Hazelnut). However, its polypeptide sequence suggests a limited similarity with other allergenic lipid transfer proteins from vegetable sources, and therefore no significant cross-reactivity (2, 3). Ole e 7 has less than 35% sequence identity with lipid transfer protein Pru p 3, from Peach (4).
The prevalence of many Olive pollen allergens is dependent on geographical location (5). Although Ole e 7 is considered to be a minor Olive pollen allergen, its prevalence has been found to vary dramatically between areas of low and high Olive pollen exposure (6). The highest allergenicity of Ole e 6 (7), Ole e 7 (1), Ole e 9 (8), and Ole e 10 (9) has been reported only in areas of intense Olive tree cultivation. High Olive pollen counts have been shown to be one of the main predictors of intensity of rhinitis and asthma symptoms in susceptible individuals during the pollen season (10). The major allergens identified (with more than 50% frequency) were Ole e 1, Ole e 7, Ole e 9, and Ole e 10. However, although the IgE-reactivity pattern involving more than 3 allergens was observed in approximately 75% of 156 patients, 45 different IgE patterns were observed when 8 allergens were tested in this group (11).
In a Spanish study of Olive pollen-allergic patients, 107 (90.7%) patients had a positive skin response to Ole e 1; 88 (74.6%) reacted to Ole e 2; 57 (47.9%) reacted to both Ole e 6 and Ole e 7; and 43 (37.8%) reacted to Ole e 3. Serum reactivity to Ole e 1 was found in 84%; to Ole e 2 in 61.3%; to Ole e 3 in 31.9%; to Ole e 6 in 39.4%; and to Ole e 7 in 41.2% of patients (12).
Similarly, in a Spanish study in Madrid evaluating the sensitisation profile of individual allergens in pollen-sensitised patients, in a region with high exposure to Olive pollen, of 891 patients utilising a panel of 13 purified allergens, Olive allergy (as measured by specific IgE to Ole e 1) was the leading pollen allergy in the area. The minor Olive allergens Ole e 7 and Ole e 9 were markers of more severe allergic illness. Profilin sensitisation was associated mainly with grass allergy, the second most prevalent pollen allergy (13).
In a study of the prevalence of minor Olive allergens in Olive-exposed areas in Spain, sensitisation to Ole e 9 and Ole e 7 were low (10.7% and 14.4%, respectively) but statistically significantly higher (over 35%) in geographical areas where Olive pollen exposure was higher. Also, the association between presence of asthma and sensitisation to Ole e 7-positive and Ole e 9-negative patients (regardless of Ole e 1 sensitisation) was statistically significant (13). In the highly-exposed areas, 40% of Ole e 1 negative patients were sensitised to Ole e 7, indicating that the two allergens behaved independently. In other areas, Ole e 7 always paralleled Ole e 1 (13, 14). The authors suggested that the fact that that the risk of having asthmatic symptoms was twice as high in patients sensitised to minor allergens made the serum-IgE test a clinically relevant marker of the Olive allergy disease. In fact, in areas where exposure was extremely high, some patients were sensitised to Ole e 7, but not to Ole e 1; this profile may be considered a different way of being allergic to Olive pollen. Specific clinical profiles for different Olive pollen allergens can appear in areas of high exposure, and stress the need for a different approach to the standardisation of Olive allergy vaccines for this population (13).
Although Ole e 7 may be regarded as a minor allergen of Olive pollen, with the exception of areas of intense cultivation (where it nevertheless shows high prevalence) it is associated with a propensity for increased clinical severity (15). A larger number of adverse reactions have been recorded in patients sensitised to Ole e 7 or Ole e 9, but not sensitised to other panallergens (15, 16).
Moreover, in a study that evaluated allergenic patterns in patients with Olive pollen allergy and fruit allergy, Ole e 7 was shown to be associated with an increased risk of food anaphylaxis, and was clearly associated with more severe clinical symptoms in patients who had had anaphylactic reactions (11, 17).
In a study that evaluated the association between sensitisation to allergens of Olive tree pollen and confirmed plant-derived food allergy, 134 patients with allergy to Olive pollen were recruited. Group A consisted of 21 patients with OAS, and Group B of 19 patients who had experienced anaphylaxis. Skin-prick testing demonstrated sensitisation to Ole e 7 more frequently in patients from group B. In patients from group B, significant association with Olive tree pollen allergens was found between positive SPT to Rosaceae fruits and Ole e 3 and Ole e 7; Cucurbitaceae and Ole e 7; and Actinidiaceae and Ole e 3 (17).
Assessing Ole e 7 may be relevant for immunotherapy: patients sensitised to Ole e 7 or Ole e 9 (but not to pollen panallergens polcalcin or profilin) have been reported to be less tolerant of immunotherapy at the recommended allergen dose (15). Considering that in extreme Olive pollen exposed areas, Ole e 7 (but not Ole e 9) is independent of Ole e 1, with 40% of Ole e 1-negative patients being sensitised to Ole e 7 (18), researchers have proposed that allergen extracts for immunotherapy should be standardised by assessing the content of relevant minor allergens (19).
Measuring Ole e 7 specifically (and in particular for epidemiological studies) may be useful, considering that extreme allergenic differences have been demonstrated between Olive pollens obtained from different cultivars. Individual allergen content of five batches of Olive pollen collected in Spain from different Olive varieties reported Ole 7 varying from 806 to 2335µg Ole e 7/g, and Ole e 9 from 1368 to 2044µg Ole e 9/g (14). This was attributed to the variability of the major IgE-binding component (20). The concentration of Ole e 9 has also been reported to vary several hundred times between different batches of Olive pollen extracts (21).
Recombinant or native allergens may be of benefit as current standard diagnostic methods utilise crude pollen extracts that contain a complex mixture of allergenic and non-allergenic proteins. Furthermore, Ole e 1 concentration has been shown to have a 25-fold variation in pollen extracts (22). Therefore, using a well-defined allergen such as nOle e 7 allows for improved diagnosis and therapy. Assessing individual allergens could substantially improve the diagnosis of sensitisation to Olive pollen, and would allow the identification of specific factors that influence clinical phenotypes in Olive tree pollen-related diseases and their natural history (11). However, Olive pollen allergy is a complex disease, involving environmental and genetic factors (11).
It is also evident that quantitation of both major and minor allergens is relevant in standardising Olive allergy reagents and vaccines.
The application of recombinant and native single allergens for clinical practice is their use in diagnosis and immunotherapy. Diagnosis based on individual allergenic components allows specific disease-eliciting allergens to be determined.
- 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.
- Florido López JF. Symposium Internacional ‘Alergia a Polen de Olivo’. Aspectos clínicoepidemiológicos. Rev Esp Allergol Inmunol Clin 1994;9(2):1-31.
- 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.
- Salcedo G, Sánchez-Monge R, Barber D, Díaz-Perales A. Plant non-specific lipid transfer proteins: an interface between plant defence and human allergy. Biochim Biophys Acta 2007;1771(6):781-91.
- Rodriguez R, Villalba M, Monsalve RI, Batanero E. The spectrum of olive pollen allergens. Int Arch Allergy Immunol 2001;125(3):185-95.
- Gonzalez EM, Villalba M, Rodriguez R. Allergenic cross-reactivity of olive pollen. Allergy 2000;55(7):658-63.
- 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.
- 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.
- 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.
- Florido JF, Delgado PG, de San Pedro BS, Quiralte J, de Saavedra JM, Peralta V, Valenzuela LR. High levels of Olea europaea pollen and relation with clinical findings. Int Arch Allergy Immunol 1999;119(2):133-7.
- 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.
- Quiralte J, Florido F, Arias de Saavedra JM, Gomez A, Saenz de San Pedro B, Gonzalez E, Rodriguez R. Olive allergen-specific IgE responses in patients with Olea europaea pollinosis. Allergy 2002;57 Suppl 71:47-52.
- 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, 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.
- 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.
- Florido Lopez JF, Quiralte Enriquez J, Arias de Saavedra Alias JM, Saenz de San Pedro B, Martin Casanez E. An allergen from Olea europaea pollen (Ole e 7) is associated with plant-derived food anaphylaxis. Allergy 2002;57 Suppl 71:53-9.
- 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, 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.
- Barber D, Carpizo J, Garcia-Rumbao MC, Polo F, Juan F. Allergenic variability in olea pollen. Ann Allergy 1990 Jan;64(1):43-6.
- 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.
- Villalba M, Batanero E, Lopez-Otin C, Sanchez LM, Monsalve RI, et al. Amino acid sequence of Ole e I, the major allergen from olive tree pollen (Olea europaea). Eur J Biochem 1993;216:863-9.
- Liccardi G, D'Amato M, D'Amato G. Oleaceae pollinosis: a review. Int Arch Allergy Immunol 1996;111(3):210-7.
- D'Amato G, Liccardi G. The increasing trend of seasonal respiratory allergy in urban areas. Allergy 2002;57 Suppl 71:35-6.
- 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.