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- Material and methods
Background: Peach allergy has two different patterns: central Europe with oral allergy syndrome (OAS) related to a primary sensitization to birch pollen Bet v 1 and profilins and southern Europe with mostly systemic symptoms, in many cases due to sensitization to lipid-transfer proteins.
Methods: Thirty peach-allergic patients with positive skin and food challenge tests and 29 control subjects were included. Skin prick tests (SPT) with inhalant allergens, commercial peach and apple extracts and native Pru p 3 were performed. In vitro specific immunoglobulin (Ig) E to grass pollen, birch pollen, peach, apple, rBet v 1, rBet v 2 and rPhl p 12 was determined by CAP, and rBet v 1, rMal d 1, rMal d 4, rMal d 3 and rPru p 3 using the ADVIA-Centaur platform. Basophil activation test (BAT) with commercial peach extract, commercial apple extract, nPru p 3, rMal d 3, rMal d 1 and rMal d 4 was also performed.
Results: Pru p 3 was the major allergen in the patient group from northern Spain. Sensitization to this allergen was found in 100% of the patients with systemic symptoms or contact urticaria. Only 60% of OAS patients were sensitized to Pru p 3, being all of them sensitized to profilins and 60% of them to allergens of the Bet v 1 family. Specific IgE determination and BAT using recombinant allergens (rPru p 3) show specificity and sensitivity values close to 100%.
Conclusions: Most peach-allergic patients coming from the north of Spain present systemic symptoms after ingestion of peach, Pru p 3 being the main allergen. Patients with OAS present profilin-Bet v 1-related sensitization. Thus, in the north of Spain our patients show a mixed central-south Europe pattern with LTP-profilin-Bet v 1 sensitization depending on the symptoms presented. The use of natural and recombinant plant allergens, allows establishing the sensitization patterns to the different allergens studied.
Peach allergy is the most frequent type of food allergy in the adult population in southern Europe (1, 2), and two clearly different clinical response patterns have been described for this food. In central Europe, oral allergy syndrome (OAS) prevails (3), whereas in southern Europe, peach allergy triggers more severe, even life-threatening reactions (4). These local differences reveal the existence of two different sensitization patterns (5, 6). In central Europe, initial birch pollen allergy influences the development of food allergy to Rosaceae, as birch allergens, mainly Bet v 1 and Bet v 2, have an important cross-reactivity with homologous proteins of Rosaceae fruits (3, 5). In southern Europe, where the presence of birch is rare, peach allergy is mediated mostly by Pru p 3, which is a lipid-transfer protein (7, 8), and sensitization to this allergen is not dependent on a previous allergy to birch pollen. Pru p 3 is a major allergen of peach in Spain (4), but it does not seem to be exclusive. Among peach-allergic patients in the north of Spain there is also a subgroup with OAS or with only contact urticaria, in an environment where the prevalence of birch pollen sensitization is rare (9). Thus, in our Atlantic climate environment (northern Spain), birch pollen represents only 2.86% of the total (589 grains of pollen/m3/year) (9). Even though this amount is low compared with the central European levels, it is higher than in other areas of our country with a continental climate, such as Madrid, where it is only around 0.10% of the total number of pollens per year (10).
The aim of this study was to analyse the different patterns of sensitization to the main Rosaceae allergens in peach-allergic patients in the southern European environment, differentiating their profile based on the clinical manifestations, as well as to validate the diagnostic potential of natural and recombinant allergens. To determine this sensitization, we used skin tests with nPru p 3 and two in vitro tests: specific immunoglobulin (Ig) E determination and flow cytometry determination of activated basophils expressing CD63, after stimulating patients’ cells with Rosaceae allergens in order to cover two different diagnostic routes, and to avoid discrepancies observed between the different in vitro diagnostic techniques for this same pathology (11). For this, both native and recombinant allergens were used, the latter not being recommended for use in vivo due to safety reasons.
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- Material and methods
The main symptom (OAS) presented by patients allergic to peach in central Europe is different from that presented by the Mediterranean patients, who show a high percentage of systemic symptoms. These data could be explained by the existence of two different patterns of sensitization to profilins/Bet v 1 homologous or LTPs, respectively, among allergic patients from the two above-mentioned geographical areas.
In the southern European environment, and particularly in the northern of Spain (Bilbao/Pamplona), patients are environmentally exposed to birch pollen, as corresponds to an Atlantic climate, with 589 grains/year of birch pollen and approximately 25% of pollen-allergic patients had a positive prick test to birch (9). However, the clinical expression of this sensitization is irrelevant. In fact, over the last 10 years, in the Allergy Service of the Basurto Hospital (Bilbao, Spain), only three desensitization treatments to this pollen have been prescribed. In contrast, more than 90% of our peach-allergic patients showed a positive skin test to Pru p 3, which was supported by positive specific IgE levels and BAT to this allergen. These results confirm the data from previous studies that point to Pru p 3, the major peach allergen in Spain and other Mediterranean areas (4, 6, 18). Sensitization to rMal d 3 was present in 90% of our group of patients. This could be because of the high structural similarity between these LTP allergens (18, 19). In fact, 50% of our patients tolerated the ingestion of apple (information obtained from the clinical interview), which corroborates this structural relationship as the cause of rMal d 3 sensitization, rather than an actual primary sensitization to apple LTP. These data are similar to the ones obtained by other authors in apple-allergic patients, being in Spain Mal d 3 the predominant allergen for this sensitization, unlike the central Europe countries where the predominant allergen in apple-allergic patients is Mal d 1. In these series, like in ours, the first triggering food is peach and subsequently it can associate other Rosaceae fruits such as apple due to the cross-reactivity of their LTPs (6). Furthermore, the sensitization to LTP is observed in 60% of our patients with OAS and 100% of patients with contact urticaria, thus suggesting that the sensitization itself is not synonymous of systemic symptoms. In fact in some central European patients monosensitized to Pru p 3 only OAS have been registered (5).
The sensitization pattern of patients with systemic symptoms and of patients with only contact urticaria, but who tolerate the ingestion of the allergen, both in vivo and in vitro, is almost the same. All of them showed a positive prick test and in vitro test (specific IgE and BAT) to Pru p 3. In contrast, sensitization to other allergens, such as Bet v 1 or profilins, is practically irrelevant in both groups (5% of the cases).
In patients with OAS, the sensitization pattern shows clear differences compared with the other two groups. Although three of the patients with OAS had a positive prick test to Pru p 3, sensitizations to two allergen families that are practically not present in the other patients were found in this group. First, all of them had sensitization to profilins (100% of the cases to rPhl p 12 and Bet v 2, 80% of the cases to Mal d 4), which indicates a high cross-reactivity between profilins of different plant foods and pollens (20, 21). In fact, in two of the profilins used by our group, Bet v 1 and Phl p 12, the sequence homology in three of their epitopes ranges from 89% to 94% (18). Secondly, an important number of patients (60%) were sensitized to Bet v 1 and its homologues. This percentage is slightly lower than the one reported in the central European population (22, 23), but clearly higher than the one presented in Central Spain in patients with Rosaceae allergy (4, 6). Moreover, only one patient had birch pollen-related symptoms. Therefore, this sensitization does not seem to be because of birch pollen exposure, which is very low in our area in contrast with central Europe. At least the sensitization to profilins is likely due to the grass pollen sensitization presented by our patients (80% had grass pollen-related rhinoconjunctivitis) (24).
The above-mentioned sensitization pattern indicates that our population is different from the one in central Europe, as demonstrated by the high percentage of LTP sensitization, which is characteristic of the Mediterranean area. However, it also shows differences with other regions within Spain, where profilin sensitization is more important (4) (20%vs 34%). On the other hand, sensitization to Bet v 1 in our patients is higher than the one registered in Central Spain (14%vs 7%), which could be because of the greater birch pollen levels in the northern region of Spain. Only five patients in our series had OAS. Because of the low prevalence of these manifestations in our environment, the conclusions obtained are limited, although it is evident that 100% of them showed positive specific IgE determination to profilins (rBet v 2, rMal d 4, rPhl p 12). The results pose only specificity problems with some grass pollen-allergic patients, who are also sensitized to profilins but present no symptoms after the ingestion of peach.
In conclusion, and according to the results of this study, we conclude that most peach-allergic patients coming from the north of Spain suffer from systemic symptoms after the ingestion of peach, Pru p 3 being the main allergen. In our series, the peach-allergic patients who present OAS show an intermediate sensitization pattern between the one presented in central and the one presented in south Europe, being the profilins the predominant allergen; furthermore 60% of them also present a sensitization to Bet v 1 or its homologues.
The future availability of recombinant or native allergens for in vitro and probably in vivo diagnosis of allergic diseases will provide tools which will improve the diagnostic reliability of these patients (25, 26). In the case of peach allergy, the possibility of determining specific IgE and/or BAT to Pru p 3 and to one of the profilins used and/or Bet v 1 homologues will allow confirmation, together with the clinical history, not only of peach allergy, but also of the responsible allergen(s). Thus, it will be able to explain the skin-systemic symptoms or OAS related to this LTP or profilin-Bet v 1 sensitization.