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Peach fuzz contains large amounts of lipid transfer protein: Is this the cause of the high prevalence of sensitization to LTP in Mediterranean countries?
Abstract
Allergy to lipid transfer protein (LTP) is quite common in the Mediterranean countries but virtually absent in Northern Europe. The reasons for this latitude-dependent distribution are unclear. One hypothesis is that peach, the primary sensitizer to LTP, may lose in part its allergenicity as a consequence of treatments (handling, brushing, washing, and packaging) preceding marketing in Northern European. Peach surface fuzz might represent a potential vehicle of LTP.
To detect LTP in peach fuzz, and compare IgE reactivity to peach fuzz and peel of sera from LTP-allergic patients.
IgE reactivity to peach peel and peach fuzz extract was measured by ELISA using sera from 2 LTP-allergic PATIENTS. Purified peach LTP was used in inhibition studies.
Both sera strongly reacted both to peach peel and fuzz but reactivity to fuzz was stronger than to peel. Pre-absorption of one serum with peach LTP caused an 87% reduction of IgE reactivity to peach fuzz extract.
Peach fuzz contains large amounts of LTP and might be a potential vehicle of this allergen causing sensitization in genetically predisposed subjects. Fuzz loss during pre-marketing handling of peaches might be at the basis of the geographic differences that characterize allergy to LTP.
... Peach-induced contact urticaria seems particularly common in Spain and Italy [21][22][23] , probably due to the high amount of allergen contained in peach fuzz. 24 However, contact urticaria from other LTP sources including asparagus 25 , melon 26 and cannabis leaves 27,28 has also been reported. These observations are in keeping with the prevalent surface distribution of the protein in plant foods. ...
... However, if this were the case one could expect that LTP allergy occurs world-wide in genetically predisposed individuals, like fish or shrimp allergy, but things are markedly different.Notably, LTP hypersensitivity is often already present in early life74 when the sensitization through the skin, facilitated by the disruption of the cutaneous barrier in children with atopic eczema, may precede the first ingestion of several foods. Percutaneous LTP sensitization may occur also in adults; for instance, many Italian peach pickers need to wear gloves during their work due to the development of contact urticaria as an occupational disease.24 Further, peach-induced contact urticaria represents the most frequent clinical expression of LTP allergy, mainly in patients who have reported the onset of systemic symptoms immediately after expo- ...
Sensitization to lipid transfer protein (LTP), the most frequent cause of food allergy in southern Europe still shows several controversial, but also intriguing aspects. Some of these include the degree of cross‐reactivity between LTPs from botanically distant sources, the definition of risk factors, the role of some cofactors, clinical outcomes, geographical differences and the identification of the primary sensitizer in different areas. This review article tries to analyze and comment on these aspects point by point suggesting some explanatory hypotheses with the final scope to stimulate critical thoughts and elicit the scientific discussion about this issue in the readership.
... Of course, we cannot exclude tout court the primary airborne sensitization to a hitherto unknown pollen source although this hypothesis seems unlikely if one considers that a large proportion of LTP allergic patients score completely negative on allergic testing for all seasonal airborne M a n u s c r i p t a c c e p t e d f o r p u b l i c a t i o n 16 allergens and do not report any respiratory allergy. However, several data have accumulated over the years suggesting a possible direct sensitization to peach LTP via the airways (40)(41)(42)(43) or the skin (44)(45)(46)(47). Again, this does not explain the geographic prevalence of this allergy, although one has to consider that for instance peach fuzz is removed from the fruits to be exported in countries where peaches are not grown (40). ...
... However, several data have accumulated over the years suggesting a possible direct sensitization to peach LTP via the airways (40)(41)(42)(43) or the skin (44)(45)(46)(47). Again, this does not explain the geographic prevalence of this allergy, although one has to consider that for instance peach fuzz is removed from the fruits to be exported in countries where peaches are not grown (40). The main producers of peaches in the world are China, Italy, Greece, Spain, and the USA (48). ...
Background.Based on the cross-reactivity between pollen lipid transfer proteins (LTPs) and the peach LTP, Pru p 3, it has been suggested that the pollen might initiate the LTP sensitization process. Objective. To establish whether LTP allergy can be considered as a pollen-food syndrome. Methods. The literature was reviewed and new data of component-resolved diagnosis from Italy obtained by both ISAC immunoassay and ImmunoCAP on large populations of LTP hypersensitive patients were provided and analyzed. Results. Among Pru p 3 reactors, patients positive for Art v 3 and Pla a 3 largely exceeded those sensitized to the respective major pollen allergens, Art v 1 and Pla a 1/Pla a 2. Pru p 3 reactivity remained stable around 80-90% at all ages, whereas Art v 3 and Ole e 7 recognition was missing in younger patients. Pru p 3 IgE exceeded IgE specific for pollen LTP at all ages. Inhibition studies carried out on LTP reactors showed that commercial extracts of mugwort and plane pollen were unable to inhibit significantly Pru p 3 IgE reactivity. In follow-up studies, baseline Pru p 3 IgE levels exceeded Art v 3 IgE levels in 84% of those sensitized to both allergens, and all patients positive to only one LTP allergen at baseline were sensitized to Pru p 3. Further, most of the patients who did not show any LTP reactivity at baseline became exclusive Pru p 3 reactors. On ImmunoCAP singleplex Pru p 3 IgE levels exceeded Art v 3 IgE levels in 89% of cases (p less than 0.0001). Most literature data were in keeping with these new observations. Conclusions. The evidence for LTP syndrome being a pollen-food syndrome is presently very thin. Our data do not rule out the possible sensitization to the protein, via the airways or the skin.
... From a standpoint of LTPs, Pru p 3 in peach allergy resembles Cor a 8 in hazelnut allergy, which is not an effective marker to diagnose allergy in Japan but an effective marker to predict allergy in Mediterranean areas. 24,25 For Mediterranean patients allergic to LTP, peach has been implicated as the primary sensitizer. 25 Conversely, few Japanese patients with peach allergy are sensitized to LTP (Pru p 3). 24 We speculate that as most Japanese children are sensitized to pollen, while few children are sensitized to LTP, both LTPs (Pru p 3 and Cor a 8) are not useful as diagnostic markers of peach and hazelnut allergies. ...
... 24,25 For Mediterranean patients allergic to LTP, peach has been implicated as the primary sensitizer. 25 Conversely, few Japanese patients with peach allergy are sensitized to LTP (Pru p 3). 24 We speculate that as most Japanese children are sensitized to pollen, while few children are sensitized to LTP, both LTPs (Pru p 3 and Cor a 8) are not useful as diagnostic markers of peach and hazelnut allergies. ...
Background:
Cor a 9 and Cor a 14 are effective markers for predicting hazelnut allergy. However, there have been no reports on the component-resolved diagnostics (CRD) of hazelnut allergy using an oral food challenge (OFC) for diagnosis in Asia. We hypothesized that CRD would improve the accuracy of diagnosing hazelnut allergies in Japanese children.
Methods:
We recruited 91 subjects (median age: 7.3 years) who were sensitized to hazelnuts and had performed a hazelnut OFC at the National Hospital Organization Sagamihara National Hospital between 2006 and 2017. All subjects were classified as allergic or asymptomatic to 3 g of hazelnuts. The sIgE levels (hazelnut/Cor a 1/Cor a 8/Cor a 9/Cor a 14/alder pollen) were measured using ImmunoCAP. We aimed to determine the predictive factors of hazelnut allergy.
Results:
Nine subjects (10%) were allergic to ≤3 g of hazelnuts. Levels of sIgE for Cor a 9 in hazelnut-allergic subjects were significantly higher than those in asymptomatic subjects (4.47 vs. 0.76 kUA/L, p = 0.039). Levels of sIgE to alder pollen and Cor a 1 in hazelnut-allergic subjects were significantly lower than those in asymptomatic subjects (<0.10 vs 13.0 kUA/L, p = 0.004; <0.10 vs 5.03 kUA/L, p = 0.025). The area under the receiver operating characteristics curve for hazelnut/alder/Cor a 1/Cor a 9 was 0.55/0.78/0.72/0.71, respectively, with p = 0.651/0.006/0.029/0.040, respectively.
Conclusions:
The findings of a high sIgE level for Cor a 9 and a low sIgE level for Cor a 1 can improve the diagnostic accuracy to better identify Japanese children sensitized to hazelnuts.
... The localisation of secreted LTPs as components of the cell wall of epidermal/hypodermal cells ensure the exposition of these allergens at the surface of these fruits. Recent results suggest that the fuzzy hairy cover of peach might account for the high prevalence of sensitisation to peach in people from Mediterranean countries (34). As a consequence Borges et al. recommended a consumption of peeled-off fruits to reduce the risk of severe allergic reactions in individuals sensitised to Rosaceae fruits (29). ...
... LTP sensitisation shows a surprisingly, and not yet fully explained, geographical distribution pattern in northern and southern European populations. Several hypothesis could explain this difference: genetic pattern of these populations, food consumption, environment of the plants culture (stress, pathogens), type and/or localisation of culture, storage and/or transport conditions, influence of the ripening, influence of technological treatments… Certain groups started to work on one or other of these problems, but it remains still much of point to solve to understand clearly this "LTP Syndrome" (34,109,110). ...
Lipid transfer proteins (LTPs) are highly conserved and widely distributed throughout the plant kingdom. Several members of LTP family have been identified as relevant allergens in food and pollens. Because of their high resistance to heat treatments and enzymatic digestion, these proteins are allergenic candidates for oral route sensitisation. This review presents biochemical features, allergenicities and cross reactivities of fruit, cereal and pollen LTPs.
... Our data revealed that the fruits exhibiting the most cross-reactivity were peach and mango, and this finding supports data reported in the literature [5,34]. Previous studies have demonstrated that the allergenicity of fruits may be affected by the selected variety and especially differences between peel and pulp [35,36]. ...
Background
Many plant food allergens have been implicated in cross-reactivities and may cause repetitive pan-allergenic exposures, which increase the severity of patients’ allergic symptoms. Identification of allergenic protein levels in food allows for more precise dietary advice. This study aimed to determine LTP, profilin, and PR-10 in the 15 most popular fruits in Taiwan.MethodscDNA encoding profilin (Sola l 1), nonspecific lipid transfer protein (nsLTP, Sola l 3), and pathogenesis-related protein (PR-10, Sola l 4) were cloned into the pQE30, expressed in Escherichia coli, and purified. Extracts of the most popular fruits, including apple, banana, carrot, celery, dragon fruit, hami melon, jujube, kiwi, mango, melon, orange, papaya, peach, persimmon, and tomato, in Taiwan were prepared in PBS. The allergenic protein levels in these extracts were determined by immuno-dot blotting using rabbit anti-rSola l 1, 3, and 4 polyclonal antibodies.ResultsAmong all 15 fruit extracts tested, peach and mango contained the highest levels of profilin, nsLTP, and PR-10. Papaya, melon, and tomato contained low but detectable levels of the three pan-allergens.Conclusion
Our data suggest that peach and mango contain the highest levels of important pan-allergens among the 15 common fruits tested, which agrees with epidemiological data.
... LTP is a widely cross-reacting Nutrients 2021, 13, 1638 5 of 35 plant panallergen. The offending food for LTP-allergic patients was most often peach, but other foods can also include other members of the Rosaceae family of fruits (apple, pear, cherry, plum, apricot, medlar, almond, and strawberry), tree nuts, corn, rice, beer, tomato, spelt, pineapple, and grape [28][29][30]. Importantly, some foods can trigger anaphylaxis with delayed onset after allergen exposure, as in the case of galactose-α-1,3-galactose (α-gal), in which reactions can occur up to 4 to 6-12 h after allergen ingestion [31]. ...
Adverse food reactions include immune-mediated food allergies and non-immune-mediated intolerances. However, this distinction and the involvement of different pathogenetic mechanisms are often confused. Furthermore, there is a discrepancy between the perceived vs. actual prevalence of immune-mediated food allergies and non-immune reactions to food that are extremely common. The risk of an inappropriate approach to their correct identification can lead to inappropriate diets with severe nutritional deficiencies. This narrative review provides an outline of the pathophysiologic and clinical features of immune and non-immune adverse reactions to food—along with general diagnostic and therapeutic strategies. Special emphasis is placed on specific nutritional concerns for each of these conditions from the combined point of view of gastroenterology and immunology, in an attempt to offer a useful tool to practicing physicians in discriminating these diverging disease entities and planning their correct management. We conclude that a correct diagnostic approach and dietary control of both immune- and non-immune-mediated food-induced diseases might minimize the nutritional gaps in these patients, thus helping to improve their quality of life and reduce the economic costs of their management.
... Вполне вероятно, что возникновение сенсибилизации у детей, проживающих на Урале, могло происходить в летний период во время отдыха в средиземноморских странах. Именно в этих географических регионах описаны тяжелые системные реакции на белки хранения и nsLTP-протеины [12]. Миграция населения России в страны Средиземноморья в отпускной период, желание родителей включать в рацион питания детей больше разнообразных фруктов и орехов (зачастую вместо кисломолочных продуктов и мяса) приводят к тому, что появляются пищевые пристрастия, не характерные для жителей Урала, меняется спектр сенсибилизации у детского населения, развиваются аллергические реакции на продукты, ранее не являвшиеся аллергенами для уральских детей. ...
Aim: to study the sensitization profile in patients with sensitivity to Bet v1 allergen who have clinically significant respiratory symptoms of pollinosis during the birch flowering season, oral allergy syndrome (OAS), and angioedema to nuts and stone fruits. Patients and Methods: a prospective open-label study included 40 children (average age 7.52±0.64), 26 (65%) boys and 14 (35%) girls. All children had sensitization to the birch major allergen (Bet v1), symptoms of respiratory allergy during the birch flowering season, manifestations of OAS with angioedema in combination with hives or without it after eating fruits of Rosaceae family/nuts/peanuts. Children underwent general clinical and allergy researches, determination of total IgE and eosinophil cationic protein. By the method of component-resolved diagnosis of allergy (ISAC-112, ImmunoCAP), a comprehensive allergology examination for 112 allergen molecules was performed for each child. Results: the children of the study group were found to have increased values of total IgE (256.66±40.45 IU/mL) and eosinophil cationic protein (67.22±8.67 ng/mL). It was found that 57.5% of children were sensitized to tree nut storage proteins (rJug r1, rJug r2, NCoR a9, rAna o2, rBer e1), and some patients (27.5%) had increased specific IgE to non-specific lipid-transfer proteins (npLTPs) (rPru p3, NCoR a8, rAra h9, rJug r3). Antibodies to peanut storage proteins (rAra h1, rAra h2, rAra h3, rAra h6) were in 22.5% of children in the study group. Conclusion: the component-resolved diagnosis of allergy allows to determine the sensitization profile of patients. Sensitization detection to storage proteins and/or nsLTPs of nuts, peanuts and fruits is a predictor of possible severe allergic reactions. The exclusion of these products, both raw and heat-treated, reduces the number of severe acute allergic reactions in patients and prevents possible fatal outcomes. KEYWORDS: oral allergy syndrome, angioedema, children, birch, sensitization to Bet v1 allergen, storage proteins, nsLTPs. FOR CITATION: Lepeshkova T.S., Beltyukov E.K., Tsarkova S.A., Naumova V.V. Oral allergy syndrome and angioedema in patients with birch allergen sensitization: are there any high risks? Russian Medical Inquiry. 2021;5(1):21–24. DOI: 10.32364/2587-6821-2021-5-1-21-24.
... 33,34 Especially the peach surface fuzz have large amounts of LTP, but also the peel and cutin layers of peaches are rich in proteins and have a higher allergenicity than the pulp with its high carbohydrate content. 35,36 Because of the geographical distribution of LTP, sensitization probably occurs through the skin or airways. Rosaceae allergic patients who are hypersensitive to LTP frequently show both skin and in-vitro cross-sensitization and cross-reactivity to many botanically unrelated fruits and vegetables. ...
Background
Naturally‐derived cosmetic product ingredients of both plant and animal origin are increasingly being included in product formulations in order to cater to consumer preferences. They may be an overlooked cause of reactions to cosmetic products in some patients with dermatitis.
Objectives
To identify naturally‐derived cosmetic product ingredients with allergenic potential (type I and type IV) and propose a cosmetic screening test series.
Methods
The study was conducted in two steps. The first step was a market survey using a non‐profit application helping consumers avoid problematic substances in cosmetic products. The application contained 10舁067 cosmetic products that were label checked for naturally‐derived cosmetic product ingredients. The second step was a literature search to examine how frequently the naturally‐derived ingredients were described and related to allergic reactions in cosmetics or other topically administered products.
Results
We identified 121 different naturally‐derived cosmetic product ingredients that were included in at least 30 cosmetic products. In total, 22 ingredients were selected for a screening test series.
Conclusions
We propose a supplemental patch test and a prick test screening series with naturally‐derived cosmetic product ingredients for patients with skin reactions to cosmetic products, aiming to identify a cause in more patients than is currently possible.
This article is protected by copyright. All rights reserved.
... Non-specific LTP (nsLTP) consists of secreted proteins, which accumulate, in the cell walls during the fruit ripening process [10]. In peach, Pru p 3 essentially accumulates in the fuzzy covering the ripe fruit [11]. As a practical consequence, peeling off the fruits before their consumption helps to significantly reduce their LTP content. ...
Anaphylactic reactions associated with the consumption of a number of fruits have been identified so far. Stone fruits belonging to the Rosaceae family have been particularly investigated in this respect, due to the occurrence of lipid transfer protein major allergens LTP, in both the pulp and the skin of the fruits. Other offending allergens like the PR-5 thaumatin-like proteins TLP, profilins and a variety of enzymes (β1,3 glucanase, chitinase) also occur in many fruits. However, stone fruits consist of another source of major allergens located in the fruit kernel, namely the cupin and 2S albumin allergens. Cupin allergens consist of three categories of seed storage proteins: germins (< 7S protein), vicilins (7S globulins) and legumins (11S globulins). All of these allergens exhibit the canonical protomeric structure made of a single (germin) or two cupin motifs (vicilin, legumin) associated to two α-helical arms. In both proteins, three identical protomeric structures become non-covalently associated by their α-helical arms to form a flattened triangle-shaped homotrimer. Germins (90 kDa) and vicilins (150 kDa) consist of a single homotrimer whereas legumins result from the non-covalent stacking of two homotrimers to form a huge hexameric structure of 300 kDa. Here, we present a catalogue of the cupin allergens distributed in the commonly consumed stone fruits. All of these cupin allergens behave as major allergens that are susceptible to trigger severe anaphylactic responses following their inadvertently consumption by previously sensitized consumers. In fact, it is noteworthy that kernels of a variety of stone fruits including apple, grape, physalis, tomato etc., are often consumed together with the pulp of the fruits. Faced with a fruit allergy, allergologists have to bear in mind the possible involvement of seed and kernel allergens in the fruit allergenic response. In this respect, both the measurement of cupin-specific IgE and the possible occurrence of allergic manifestations cross-linked to the consumption of other cupin-containing foods, should be useful to assess the severity of the fruit allergy, and to decide on the most appropriate management and treatment for this allergy.
... 23 The essential role of peach fuzz in causing histamine release following contact with the skin has been suggested by the absence of any skin reactivity following skin rubbing with nectarine, a fruit that is genetically identical to peach but whose surface is bald. 24 In effect, peach fuzz contains large amounts of LTP 25 and it cannot be excluded that the skin represents a major pathway leading to sensitization to the protein. The oral allergy syndrome (ie, the occurrence of itching and tingling of the lips, oral mucosa, tongue, and upper airways immediately after ingesting the offending food) is probably the most frequent clinical expression of LTP hypersensitivity. ...
Despite a huge number of studies, many aspects of the lipid transfer protein (LTP)-syndrome, the most frequent primary food allergy in Mediterranean countries, remain unclear. Its peculiar geographical distribution, along with the extreme variability of its clinical expression make this type of food allergy something unique in the panorama of IgE-mediated food-induced allergic reactions. The present review article tried to summarize the current knowledge about the most important aspects of LTP sensitization and allergy, along with the importance of positive and negative co-factors in the clinical expression of the syndrome as well as the issues regarding the cross-reactivity between LTPs present in botanically related and unrelated foods. Further, the possible absence of the protein from some plant foods is discussed.
... LTP cross-reactivity is often accompanied by clinical food allergy, frequently including systemic reactions [32]. Finally, peach has been identified the primer sensitizer to Pru p 3 [33]. ...
Background
Pollen allergy may be frequently associated with fruit-vegetables: the so-called pollen food syndrome. Pru p 3 is the most relevant peach allergen. Previously, it has been reported that serum specific IgE level to Pru p 3 depends on age in a limited geographic area.
Objective
This study aimed to to test the hypothesis about the differences of Pru p 3 sensitization across Italy, mainly concerning the impact of age.
Methods
The current study was retrospective and multicentre, involving 2 labs in Northern Italy (709 subjects), 1 in Genoa (1,040 subjects), and 1 in Southern Italy (2,188 subjects). All of them referred to labs for IgE testing because of suspected food allergy. Serum IgE to Pru p 3 was assessed in all subjects.
Results
Sixteen point seven percent (16.7%) of subjects were sensitized to Pru p 3. Sensitization percentage sigificantly decreased over time. The serum IgE levels increased up to young adulthood and then decreased until aging.
Conclusion
Our experience demonstrates that Pru p 3 sensitization and production are closely age-dependent phenomena.
... Оказалось, что основное связывание IgE-антител (до 87%) происходит с экстрактом из волосков, что подтверждает предположение о доминирующей концентрации Pru p 3 в волосках, покрывающих поверхность фруктов. Авторы предположили, что редкая встречаемость системных реакций на персик у жителей Северной Европы, по сравнению с жителями Южной, связана с различными химическими обработками, которым подвергаются фрукты при транспортировке и хранении [3]. Таким образом, если в странах Северной Европы и России Pru p 3 является минорным аллергеном, то для жителей стран Средиземноморья он -мажорный аллерген, занимающий лидирующее место виновного агента, провоцирующего развитие системных и анафилактических реакций. ...
Results of immunological and molecular biology investigations over last decades allowed clear to specify mechanisms of development and clinical features of allergic reactions to food of plant origin, including allergies to fruits Prunus persica - peaches and nectarines. The article contains the analysis of literature data on allergic reactions to peach, as well as clinical observations of the patients with this kind of allergy and of the results of the component component resolved diagnosis, ISAC ImmunoCAP, conducted by these patients. The collected data allow to detect two fundamentally different types of allergic reactions to Prunus persica. This is due to sensitization to allergen Pru p 3 severe systemic reaction, and due to sensitization to Pru p 1 or Pru p 4 – local response, manifesting oral allergy syndrome and associated with sensitization to pollen allergens.
... The reason for the strange geographical distribution of allergy to LTP, which is nearly exclusive of the Mediterranean countries [23], has long been a matter of debate. Some studies suggested that the fuzz of untreated peaches might be a relevant source of LTP and that sensitization may occur through the skin [24] or through the airways [25], but this still remains an open question. The findings in our small population of patients o12 years old confirm that LTP sensitization is typically found in southern Italy and clearly suggest that it may occur early in life. ...
BACKGROUND:
Studies of the prevalence of different types of food allergy in adults are lacking.
OBJECTIVE:
To define the prevalence of IgE-mediated food allergies in Italian adults attending allergy clinics and to assess possible differences associated with geographical position and/or dietary habits.
METHODS:
Seventeen allergy outpatient clinics scattered throughout Italy participated to a multi-centre study in 2007. The number of atopic subjects and of food allergic patients along with clinical features were recorded by pre-defined criteria. Patients with unequivocal history of food allergy confirmed by positive skin prick test were included as cases.
RESULTS:
Twenty five thousand six hundred and one subjects were screened; 12,739 (50%) were atopic, and 1079 (8,5%) had IgE-mediated food allergy. Sixty four percent of patients were females. Overall, the most frequent food allergy was the pollen-food allergy syndrome (55%), which was associated with oral allergy syndrome in 95% of cases and whose frequency decreased southbound. Forty-five percent of patients had a type 1 food allergy, in most cases (72%) caused by fruits and vegetables, and generally associated with a history of systemic symptoms. Type 1 food allergies represented 96% of food allergies in the South. Lipid transfer protein (LTP) accounted for 60% of sensitizations and caused most primary food allergies in all areas.
CONCLUSION:
Plant-derived foods cause most food allergies in Italian adults. The pollen-food allergy syndrome is the most frequent type of food allergy followed by allergy to LTP whose frequency increases southbound. The pattern of allergy to certain foods is clearly influenced by specific geographic features such as pollen exposure and dietary habits.
... Pru p 3 is an abundant component of peach peel and displays a high thermal and protease resistance. It is also well known as an important peach allergen that has been associated to severe allergic reactions to fruit ingestion and has received an in-depth characterization, including structural and immunological comparison with homologs from different allergenic sources (Asero et al., 2006;Bernardi et al., 2011;Brenna, Pastorello, Farioli, Pravettoni, & Pompei, 2004;Cavatorta et al., 2009;Ciardiello et al., 2010;Lleonart, Cistero, Carreira, Batista, & Moscoso del, 1992;Schulten et al., 2011;Tordesillas et al., 2009). ...
Abstract
Food allergy is an important public health and safety concern. The description of the pattern of individual allergens associated to each food is of crucial importance both for the diagnostic process and the setting of a safe diet for each allergic subject. However, we are still far from this goal as can be seen from allergen data resources like Allergome. Although some advances have been made during the last few years leading to the identification of new allergens in many allergenic sources and to their characterization, this knowledge is still fragmentary and does not allow the definition of a comprehensive pattern. The exploitation of new technologies and the improvement of those already existing has provided significant contributions, although the widespread use of specific technologies and/or methodologies without cross-checks between them may have generated some biases leading to the preferential identification of selected subsets of allergenic molecules. It would be now desirable to adopt new strategies based on a dynamic combination of different methodologies, spanning from the classic biochemistry-based ones to the innovative microtechnologies and bioinformatics, in order to obtain the best results and give a forward thrust to knowledge in this field.
... These results are in good agreement with a predominant presence of LTP1 in peel in comparison with pulp, which was previously found for the peach fruit by analysing the specific mRNA distribution or by the direct quantification of the protein using specific antibodies (Botton et al., 2002;Botton et al., 2009;Brenna et al., 2004;Carnes et al., 2002). In the case of peach, a high concentration of Pru p 3 in fuzz was also determined (Asero et al., 2006); this specific localization of the allergenic protein in peach is likely to be responsible for a recently described respiratory allergy caused by LTP1 (Borghesan et al., 2008;Palacin et al., 2007). All these data are in good agreement with the results of clinical studies, demonstrating a higher allergenicity of peel in comparison with pulp for Rosaceae fruits (Fernandez-Rivas and Cuevas, 1999;Fernandez-Rivas et al., 1997). ...
Non-specific lipid transfer proteins belonging to LTP1 family represent the most important allergens for non pollen-related allergies to Rosaceae fruits in the Mediterranean area. Peach LTP1 (Pru p 3) is a major allergen and is considered the prototypic allergenic LTP. On the contrary, pear allergy without pollinosis seems to be under-reported when compared to other Rosaceae fruits suggesting that the as-yet-uncharacterized pear LTP1 (Pyr c 3) has in vivo a low allergenicity. We report here on the identification of four cDNAs encoding for LTP1 in pear fruits. The two isoforms exhibiting amino acid sequences most similar to those of peach and apple homologues were obtained as recombinant proteins. Such isoforms exhibited CD spectra and lipid binding ability typical of LTP1 family. Moreover, pear LTP1 mRNA was mainly found in the peel, as previously shown for other Rosaceae fruits. By means of IgE ELISA assays a considerable immunoreactivity of these proteins to LTP-sensitive patient sera was detected, even though allergic reactions after ingestion of pear were not reported in the clinical history of the patients. Finally, the abundance of LTP1 in protein extracts from pear peel, in which LTP1 from Rosaceae fruits is mainly confined, was estimated to be much lower as compared to peach peel. Our data suggest that the two isoforms of pear LTP1 characterized in this study possess biochemical features and IgE-binding ability similar to allergenic LTPs. Their low concentrations in pear might be the cause of the low frequency of LTP-mediated pear allergy.
... The first patient had symptoms including anaphylaxis to fruits of the Rosaceae family (peach and cherry) and rhinitis symptoms attributed to plane tree and mugwort pollen sensitization. Hypersensitivity to peach is usually not associated with any kind of particular pollinosis in southern Europe, 17 and the main reactions in the Mediterranean area are directed to nsLTPs.Peach nsLTP (Pru p 3) is a major allergen in the South of Europe, being involved in over 60% of patients allergic to peach in the Spanish population. 18 In peach-allergic patients who have experienced systemic reactions, up to 100% were sensitised to nsLPTs. ...
Component-resolved diagnosis and microarray technology have been recently introduced into clinical allergy practice, and may be particularly useful in poly-sensitized allergic patients.
We compare the clinical usefulness of a microarray-based IgE detection assay (ISAC(®)) with skin tests and specific IgE with standard allergens (sIgE) or their monocomponents in four case reports of patients poly-sensitized to aeroallergens and food.
Case 1: a woman with rhinitis, oral allergy syndrome to several fruits and anaphylaxis to cherry. Diagnostic tests supported non-specific lipid transfer proteins (nsLTPs) primary sensitization. Case 2: a woman with exercise-induced asthma, rhino-conjunctivitis and oral allergy syndrome to fresh fruits of different families. A diagnosis of primary grass and weed pollen allergy with profilin and pathogenesis-related protein family 10 (PR-10) cross-reactive food allergy was proposed. Case 3: a man with atopic eczema, asthma, rhinitis, and multiple anaphylactic episodes with cashew nuts and oral allergy syndrome to fruits. The diagnostic workup supported a primary birch pollen allergy with PR-10 and nsLTPs cross-reactive food allergy. Case 4: a woman with rhino-conjunctivitis, per-operative anaphylaxis due to latex and recent pharyngeal angio-oedema episodes. The diagnosis was a primary grass and weed pollen allergy with equivocal profilin sensitization and no obvious cross-reactivity mediated by nsLTPs sensitization.
The possibility to carry out multiple sIgE measurements with single protein allergens, in particular with the microarray technique, is a useful, simple and non-invasive diagnostic tool in complex poly-sensitized allergic patients.
... In addition to ingestion and inhalation, skin contact has been proposed as a third route of LTP exposure. For example, the high allergen content in peels and cutin layers of fresh fruits has been proposed to be responsible for transdermal sensitization and peach-induced urticaria [25]. However, sensitization to Hev b 12 was shown to have no clinical relevance in contact allergy to natural rubber latex [26]. ...
Nonspecific lipid transfer proteins (LTPs) are important allergens in fruits, vegetables, nuts, pollen, and latex. Despite their wide distribution throughout the plant kingdom, their clinical relevance is largely confined to the Mediterranean area. As they can sensitize via the gastrointestinal tract, LPTs are considered true food allergens, and IgE reactivity to LTPs is often associated with severe systemic symptoms. Although Pru p 3 represents the predominant LTP in terms of patients' IgE recognition, the contribution of pollen LTPs in primary sensitization cannot be ruled out. Due to structural homology, LTPs from different allergen sources are generally IgE cross-reactive. However, sensitization profiles among allergic patients are extremely heterogeneous, and individual cross-reactivity patterns can be restricted to a single LTP or encompass many different LTPs. Molecule-based approaches in allergy research and diagnosis are important for better understanding of LTP allergy and could assist clinicians with providing adequate patient-tailored advice.
... As sensitization to LTPs is still a matter of debate, alternative routes for peach LTP, e.g. via the respiratory tract through fruit tree pollen, air-dispersed food particles, or peach leaves and even via the transdermal route, have been proposed (Asero et al., 2006; Borghesan et al., 2008; Garcia et al., 2004). However, whether LTP from foodstuff or pollen is the sensitizing molecule is hard to determine and clearly remains species-specific (Lauer et al., 2007 ). ...
Plants of the genus Artemisia domestic in Northern and Central Europe, USA and parts of Asia are a major cause of allergic symptoms from late summer to autumn. Art v 1, the major mugwort pollen allergen appears as two-domain glycoprotein, consisting of an N-terminal defensin-like and a proline/hydroxyproline-rich C-terminal part. Patients sensitized to Art v 1 commonly display IgE antibodies against the cysteine-stabilized defensin fold. Site-directed mutagenesis of eight cysteines was used to disrupt disulfide bonds to generate molecules with altered IgE-binding capacity. Engineered constructs were expressed in E. coli and recombinant proteins were tested for their allergenic and T cell reactivity as well as for their physicochemical characteristics. Three cysteine variants (C22S, C47S, and C49S) exhibited extremely low IgE-binding activity in immunoblot and ELISA using sera from Art v 1-allergic patients. Mediator release assays using rat basophil leukemia cells showed that these variants displayed a 1x10(5)-fold reduced allergenic potency as compared to wild-type protein. All variants were able to activate allergen-specific T cells in PBMC, as well as Art v 1-specific T cell lines and clones. Variant C49S displayed an increased hydrophobic surface potential which correlated with an advanced activation of allergen-specific T cells. The low allergenicity and high immunogenic activity of Art v 1 variant C49S renders the molecule an attractive candidate for hypoallergen-based immunotherapy of Artemisia pollen allergy.
... Sensitization to certain pollens containing LTP has been suggested as a possible cause [30,31] , but clear evidence is still missing. Skin contact with or inhalation of particles of peach fuzz containing large concentrations of the protein have been suggested as an alternative hypothesis to explain the geographical differences of this type of allergy [32,33] . Notably, previous studies did not observe significant differences in the amount of peaches consumed in European countries where allergy to LTP is frequent or virtually absent [34] . ...
Data about food-induced anaphylaxis in Italy are missing. Objective: It was the aim of this study to detect the main foods/food allergens causing anaphylaxis in Italy.
The frequency of anaphylaxis and the relative importance of many offending foods were assessed in 1,110 adult patients with food allergy diagnosed by common criteria at 19 allergy centres scattered throughout Italy from 1 January to 31 December 2007.
Fifty-eight of 1,110 (5%) food-allergic patients experienced at least 1 episode of anaphylaxis. On average, they were older than other food-allergic patients (34 vs. 31 years; p < 0.05). The majority of anaphylactic episodes occurred in patients sensitized to lipid transfer protein (LTP; n = 19), followed by shrimp (n = 10), tree nuts (n = 9), legumes other than peanut (n = 4), and seeds (n = 2); peanut, spinach, celery, buckwheat, wheat, avocado, tomato, fish, meat, and Anisakis caused an anaphylactic reaction in single patients. Among LTP-hypersensitive patients, peach caused 13/19 anaphylactic episodes. Shrimp-allergic patients were significantly older than other patients with food-induced anaphylaxis (p < 0.05), whereas patients allergic to LTP experienced their anaphylactic episodes at a younger age (p < 0.001). The frequency of anaphylaxis among patients sensitized to LTP, shrimp or tree nuts did not differ between northern and central/southern Italy.
LTP is the most important allergen causing food-induced anaphylaxis in Italy, peach being the most frequently offending food. Peanut-induced anaphylaxis seems very uncommon. Geographic and environmental differences both between Italy and other countries and within Italy seem to play a relevant role in the pattern of sensitization to foods.
... As sensitization to LTPs is still a matter of debate, alternative routes for peach LTP, e.g. via the respiratory tract through fruit tree pollen, air-dispersed food particles, or peach leaves and even via the transdermal route, have been proposed (Asero et al., 2006; Borghesan et al., 2008; Garcia et al., 2004). However, whether LTP from foodstuff or pollen is the sensitizing molecule is hard to determine and clearly remains species-specific (Lauer et al., 2007 ). ...
Art v 3, the lipid-transfer protein (LTP) of Artemisia vulgaris pollen is a relevant allergen showing frequent cross-reactivity with homologues in other plants. Here we report the identification of four full-length Art v 3 sequences obtained by cDNA cloning using mass spectrometry-based sequencing. Two isoforms, Art v 3.0201 and Art v 3.0301 were expressed as soluble proteins in Escherichia coli Rosetta-gami B(DE3) pLysS using different expression systems. Purified natural and recombinant Art v 3 demonstrated similar secondary structures in circular dichroism analysis. All preparations showed high thermal stability but low resistance to gastric digestion with pepsin. Patient-specific IgE reactivity patterns to natural or recombinant isoallergens were observed among Art v 3-sensitized subjects. Using Immuno Solid-phase Allergen Chip (ISAC) assays, frequent cross-reactivity of Art v 3 with LTPs from peach and hazelnut was shown. The biological activity of both isoforms was comparable to the natural allergen in basophil release assays. The newly identified sequences provide the basis for recombinant mugwort LTP production enabling batch-to-batch reproducibility and thus ensuring high-quality products for diagnosis and therapy.
... In this respect, anaphylactic responses such as contact urticaria and oral allergy syndrome have been observed in sensitized Spanish patients just after a skin contact with peach fruits in relation, most probably, with the high nsLTP content of the downy hairs covering the fruits [29]. Recent results suggest that the fuzzy hairy cover of peach might account for the high prevalence of sensitization to peach in people from Mediterranean countries [30]. As a practical consequence, both the handling and consumption of previously peeled-off peach or apple fruits should be recommended to weakly sensitized people to significantly reduce the risk of a severe allergic disease. ...
The localization and distribution of non-specific lipid transfer proteins (nsLTP) allergens in the skin and pulp of Rosaceae fruits (apple, peach, apricot, plum) has been investigated. nsLTP essentially concentrate in the pericarp of the fruits whereas the pulp contains lower amounts of allergens. Immunolocalization showed they are primarily located in the cytosol but are subsequently excreted and finally accumulate at the plasmalemma-cell wall interface and in the cell wall. However, high discrepancies were observed in the content of allergens among, e.g. different cultivars of apple. As a consequence, the consumption of peeled-off fruits is recommended to reduce the risk of severe allergic reactions (anaphylactic shock) in individuals sensitized to Rosaceae fruits.
Fruit allergy has become a health problem with regard to food safety and quality of life. Breeding and selection of hypoallergenic fruit cultivars is an efficient way to counteract allergy. This chapter reviews the prevalence of fruit allergy, common symptoms, and fruit species involved and their corresponding allergen proteins. Advancements in their linkage map positions and gene expression in fruit tissue are summarized, and genomic sequencing of apple and peach allergen genes. The genetic basis of cultivar differences in apple allergenicity has been illustrated in particular. Strategies to produce hypoallergenic fruits through conventional breeding and marker-assisted selection are discussed.
Food allergy is caused by immunologically mediated over-reactivity against food components, and may be IgE mediated or non-IgE mediated. The most serious form and the one of concern for regulatory authorities, is IgE-mediated food allergy. Food intolerances often have unknown mechanisms. However, lactose intolerance and fructose intolerance are caused by known enzyme deficiencies, and gluten intolerance is caused by an autoimmune reaction elicited by gluten protein. IgE-mediated food allergy often occurs together with skin allergy and respiratory allergy. The diagnosis of food allergy rests on three pillars: the case history, the demonstration of a specific IgE against the food in serum or by skin-prick testing, and food challenge. Testing alone will grossly overestimate the presence of a clinically manifest food allergy. The diagnosis of food allergy is often difficult and resource-demanding. Food allergy is most common in small children, but may be underestimated in young adults. There are geographical variations with regard to prevalence and which foods represent the most common allergens. Epidemiological data on food allergy are often uncertain. No validated animal models of food allergy exist. Prediction of allergenicity of a new protein depends on the overall weight of evidence derived from several sources, including comparison to known allergens in allergen databases.Keywords:food allergy;diagnosis;symptoms;prevalence;food allergen;allergenicity;animal model;gluten intolerance;lactose intolerance;fructose intolerance
Food allergy affects 1.4 to 3.7% of adults, with a feminine predominance. It is expressed only when several factors are present. In this article, we analyze the published data. The influence of climate, occupational exposure, exercise, certain drugs and addiction is emphasized. A combination of several factors was frequently observed.
Premesse
Le reazioni allergiche alla soia e alle arachidi sono in grande espansione e sono spesso gravi a causa della presenza di molecole a elevato potere antigenico, quali le LTP e le proteine di deposito. Nella soia le IgE specifiche (sIgE) vs Gly m 5 e Gly m 6 sono indicative di una sensibilizzazione primaria che può essere responsabile di reazioni anafilattiche, mentre sIgE vs Gly m 4 (PR-10) depongono per una sensibilizzazione primaria alle fagales generalmente associata a SOA. Nelle arachidi Ara h 1, Ara h 2, e Ara h 3 sono markers di sensibilizzazione genuina e rappresentano un elevato rischio di reazioni sistemiche gravi, cosÌ come le sIgE vs Ara h 9 (LTP) possono causare reazioni severe in aggiunta a SOA. Attualmente l’uso della diagnostica molecolare permette di distinguere forme di allergia primaria verso questi alimenti da forme dovute a cross reattività, ottenendo un miglior inquadramento clinico del paziente associato a un corretto giudizio prognostico.
Metodi
È stata eseguita la diagnostica molecolare in due gruppi di soggetti, il primo costituito da 10 pazienti allergici alla soia e il secondo da 11 allergici alle arachidi, prevalentemente di età pediatrica e di ambedue i sessi. Per il dosaggio delle IgE specifiche è stata utilizzata la tecnologia ImmunoCAP® (Phadia® 250. Phadia AB, Uppsala, Sweden). I risultati sono stati quantitativamente espressi in kUa/L di IgE allergene specifiche.
Risultati
Nei 10 soggetti allergici alla soia 2 hanno presentato alti livelli di IgE solo per Gly m 4, 1 solo per Gly m 5; in 4 casi è stata riscontrata una positività a entrambe le proteine di deposito Gly m 4 e Gly m 5, associata alla presenza di IgE vs l’LTP (Gly m 1 omologa). Tra gli 11 positivi alle arachidi, 5 sono risultati primariamente sensibilizzati ad Ara h 1, Ara h 2 e Ara h 3, in 4 la presenza della sensibilizzazione vs queste proteine era associata ad alti livelli di IgE vs l’Ara h 9, mentre in due pazienti erano presenti solo IgE vs l’LTP.
Conclusioni
Il nostro studio, sebbene limitato a pochi casi, conferma la variabilità di sensibilizzazione vs la soia e le arachidi. Nei pazienti allergici alla soia le reazioni più gravi si sono verificate in quelli con sIgE vs Gly m 5 e Gly m 6, cosÌ come tutti i pazienti positivi alle proteine di deposito delle arachidi hanno avuto reazioni severe in seguito a ingestione delle stesse, indipendentemente dalla presenza di sIgE vs LTP. Pertanto si può affermare che la diagnostica estrattiva non è più sufficiente, ma occorre accertare vs quale proteina specifica sia sensibilizzato il paziente per prevenire la comparsa di reazioni gravi in seguito all’ingestione dell’alimento.
Lipid transfer proteins (LTP) are produced by many plants, being present in pollen, fruit and other parts of plants. They are the leading panallergens, the most important one being peach LTP (Pru p 3). The list of sources of these allergens grows longer each day, with numerous cross-reactions, even if the origin of the sensitization (airway, digestive or cutaneous) remains unknown. LTP are involved in respiratory allergies, especially occupational ones. They are especially strong food allergens since they are thermostable and resistant to proteolysis and they can cause severe systemic reactions. In the Mediterranean region, they are the major allergens implicated in food allergy to fruit.
The principal allergens of Rosaceae (Prunoideae) fruit consist of Pathogenesis-Related proteins (PR proteins) which are essentially expressed in response to attacks on the plant by a phythopathogenic fungus. They include Lipid Transfer Proteins (LTP) of the PR-14 family, 1,3β-glucanases of the PR-2 family, and Thaumatin-Like Proteins (TLP) of the PR-5 family. Apple LTP (Mal d 3) is mainly located in the skin of apple, including the skin of several apple cultivars, i.e., Granny Smith, Golden delicious, and Fuji, which are particularly rich in LTP; the pulp of this fruit contains much less LTP. The LTP of the peach, Pru p 3, essentially concentrates in the downy hairs covering the fruit. As a practical consequence, peeling this fruit reduces considerably the amount of LTP to which sensitized individuals would be exposed. Conversely, cooking the fruit is of no interest because of the extreme resistance of LTP to thermal denaturation. In other Prunoideae fruits, e.g., plum (Pru d 3) and apricot (Pru ar 3), the LTP content of the skin and pulp of these fruits is very similar, so that peeling them does not reduce their allergenicity. Preliminary results suggest that fruit produced in biological farming have a higher LTP content compared to fruit produced in conventional farming. In Mediterranean countries, especially Spain and Italy, allergy to peach (Pru p 3) is often responsible for severe anaphylactic reactions.
Food allergies, defined as an immune response to food proteins, affect as many as 8% of young children and 2% of adults in westernized countries, and their prevalence appears to be rising like all allergic diseases. In addition to well-recognized urticaria and anaphylaxis triggered by IgE antibody-mediated immune responses, there is an increasing recognition of cell-mediated disorders such as eosinophilic esophagitis and food protein-induced enterocolitis. New knowledge is being developed on the pathogenesis of both IgE and non-IgE mediated disease. Currently, management of food allergies consists of educating the patient to avoid ingesting the responsible allergen and initiating therapy if ingestion occurs. However, novel strategies are being studied, including sublingual/oral immunotherapy and others with a hope for the future.
Purpose of review:
Nonspecific lipid transfer protein (LTP) is the main cause of primary food allergy in adults living in the Mediterranean area. The way allergic patients get sensitized to this protein is all but established, and the clinical expression of sensitization is extremely variable, ranging from long-lasting symptomless sensitization to severe anaphylaxis. Such variability is seemingly due to the presence/absence of a number of cofactors.
Recent findings:
The possibility that LTP sensitization occurs via the inhalation of LTP-containing pollen particles seems unlikely; in contrast, peach particles containing the protein seem able to sensitize both via the airways and the skin. Cosensitization to pollen allergens as well as to labile plant food allergens makes LTP allergy syndrome less severe. In some LTP sensitized subjects clinical food allergy occurs only in the presence of cofactors such as exercise, NSAIDs, or chronic urticaria.
Summary:
Lipid transfer protein allergy syndrome shows some peculiarities that are unique in the primary food allergy panorama: geographical distribution, frequent asymptomatic sensitization, frequent need for cofactors, and reduced severity when pollen allergy is present. Future studies will have to address these points as the results may have favorable effects on other, more severe, types of food allergy.
Plant lipid transfer proteins (LTPs) are ubiquitous proteins that are found in divergent plant species. Although the exact function of LTPs is not fully understood, LTPs are conserved across a broad range of plant species. Because LTPs share structural features, there is an increased probability for significant allergic cross-reactivity. The molecular features of LTPs also decrease the probability of degradation due to cooking or digestion, thereby increasing the probability of systemic absorption and severe allergic reactions. LTP allergy, unlike other forms of anaphylaxis, tends to occur more frequently in areas of lower latitude. The geographic distribution of LTP allergy, along with evidence of increased sensitization after respiratory exposure, has led to the hypothesis that LTP-related food allergy may be secondary to sensitization via the respiratory route. Clinical reactions associated with LTPs have broad clinical phenotypes and can be severe in nature. Life-threatening clinical reactions have been associated with ingestion of a multitude of plant products. Component-resolved diagnosis has played a significant role in research applications for LTP allergy. In the future, component-resolved diagnosis may play a significant role in day-to-day clinical care. Also, quantitative analysis of LTPs in foodstuffs may allow for the identification and/or production of low-LTP foods, thereby decreasing the risk to patients with LTP allergy. Furthermore, sublingual immunotherapy may provide a therapeutic option for patients with LTP allergy.
We analysed the temporal and spatial transcript expression of the panel of 18 putative isoallergens from four gene families
(Pru p 1–4) in the peach fruit, anther and leaf of two melting cultivars, to gain insight into their expression profiles and to identify
the key family members. Genotypic variation of abundantly expressed genes in mature fruit was further screened in nine additional
melting cultivars. In the Pru p 1 family, Pru p 1.01 and Pru p 1.06B were predominant and constitutively expressed in all the tissues, with large difference among cultivars observed in mature
fruits. Pru p 1.02 was especially abundant only in the leaf. A new member of the Pru p 1 family, Pru p 1.06D, was identified through peach genome mining. In the Pru p 2 family, Pru p 2.01B was predominant in all tissues, whereas Pru p 2.01A was abundant in a few cultivars and undetectable in others. Pru p 3.01 was the most highly expressed member in all tissues except the mesocarp, while the other two members exhibited tissue specificity:
Pru p 3.02 was highly expressed in the leaf, and Pru p 3.03 in the anther. Both Pru p 4 isoallergen genes were equally expressed in all tissues of both cultivars. There was high expression variability of Pru p 1 and Pru p 2 members in mature fruits among 11 cultivars, while relative lower for Pru p 3 and Pru p 4. The location, arrangement and features of peach isoallergen genes on the peach genome scaffolds were illustrated.
KeywordsGene expression–Peach allergen–Genotypic variation–Real-time PCR
Food-induced anaphylaxis (FIA) is a serious allergic reaction that may cause death rapidly in otherwise healthy individuals. There is no universal agreement on its definition or criteria for diagnosis. Hospital admissions for FIA have more than doubled in the last decade. Food is one of the most common causes of anaphylaxis, with most surveys indicating that food-induced reactions account for 30% to 50% of cases. The most commonly implicated foods are peanut, tree nuts, milk, eggs, sesame seeds, fish, and shellfish. The only life-saving treatment for anaphylaxis is allergen avoidance, and epinephrine injection if an anaphylactic event occurs.
Lipid transfer proteins (LTP) are pan-allergens in plant derived foods that have been also detected in several pollens. The observed cross-reactivity between pollen and plant-food LTPs has led to hypothesize that primary sensitisation to this allergen may occur through the airways.
The present study looked at the prevalence of hypersensitivity to different L TP-containing pollen sources among peach-allergic subjects sensitized to LTP.
Sixty-six adults (M/F 25/41; mean age 33.7 yrs) with allergy to peach LTP living in the area of Milan underwent SPT with mugwort, plane and olive pollen extracts. IgE to the same allergen sources as well as to peach were measured in 16 cases.
Skin tests with Artemisia, Platanus, and Olea pollen extracts scored positive in 16 (24%), 10 (15%), and 10 (15%) patients, respectively. Peach-specific IgE were detected in 16/16 patients, whereas IgE to Artemisia, Platanus, and Olea pollen were found in 7 (44%), 10 (62%), and 8 (50%) cases. In all cases peach-specific IgE levels were higher than levels of IgE to the three pollens, and a strong correlation between peach-specific IgE levels and the levels of IgE specific for mugwort (r = 0.84; p < 0.001) and plane (r = 0.96; p < 0.001) pollen was recorded.
In northern Italy olive, plane, and mugwort pollen seem an unlikely source of LTP sensitisation and the most likely primary sensitizer to this protein remains the peach.
Peach-induced contact urticaria is frequent in peach-allergic subjects.
It was the aim of this study to detect whether contact urticaria is associated with a specific peach allergen.
Ninety-two peach-allergic subjects were studied. Patients were diagnosed as being sensitized to lipid transfer protein (LTP; Pru p 3) or as having a pollen-food allergy syndrome induced by Pru p 1 and/or profilin, Pru p 4, on the basis of the results of a skin prick test containing these allergenic proteins in an isolated form. Specific IgE to peach extract was measured as well. Contact urticaria was confirmed by a contact test with intact, untreated peach. A contact test with nectarine was carried out as control.
Overall, contact urticaria was present in 21% of patients; the peach contact test scored positive in all cases. Contact urticaria was significantly more frequent in patients hypersensitive to LTP (63%) than in subjects with pollen-food allergy syndrome (6%; p < 0.001) and was not associated with a higher level of peach-specific IgE. In several cases, contact urticaria preceded the onset of food allergy by years. The contact test with nectarine scored negative in 5/5 cases.
Although the peach contact test was not performed in all subjects, and peach allergy was not confirmed by oral challenges, this study shows that peach-induced contact urticaria is associated with sensitization to peach LTP. The negative clinical history and contact test with nectarine along with the well-known high concentration of LTP in peach fuzz suggest that peach fuzz plays a role in the pathogenesis of contact urticaria.
It is widely accepted that, under normal conditions, the contact between allergens and the immune system via the gut results in immune tolerance. Thus, it is rather surprising that normal adults may become sensitized to foods that they have consumed a number of times without any consequence. However, the medical literature is crowded with reports suggesting that sensitization to food allergens may occur outside the intestinal tract in many instances. The present article reviews and discusses current data suggesting, either directly or indirectly, a possible initiation of food allergy in the respiratory tract or in the skin in the light of recent findings about mechanisms of tolerance and sensitization.
Peach is a common food allergen source throughout Europe. The aim of this study was to characterize peach allergy in a Portuguese patient population.
Thirty peach-allergic patients confirmed by double-blind placebo-controlled food challenges and 29 controls were included. All subjects completed a standardized questionnaire regarding symptoms and epidemiologic characteristics, skin prick tests with inhalant allergens and foods as well as specific IgE antibodies to peach, recombinant peach allergens rPru p 1, rPru p 3, rPru p 4 and cross-reactive carbohydrate determinants.
Thirty-seven percent of patients reported only oral allergy syndrome, while 37% reported generalized urticaria and/or angioedema, 17% localized contact urticaria and 10% anaphylaxis with peach. Sensitization to other Rosaceae fruits and tree nuts was present in 90 and 77% of the patients, respectively. Respiratory allergy history was associated with less severe symptoms (oral allergy syndrome or contact urticaria; p < 0.01) and positive skin prick test to peach peel or plum with more severe symptoms (urticaria and/or angioedema or anaphylaxis; p < 0.05). Ninety-seven percent were sensitized to Pru p 3, 13% to Pru p 4, 3% to Pru p 1 and 10% to cross-reactive carbohydrate determinants. Pru p 3 specific IgE was associated with Artemisia vulgaris sensitization and tree nut allergy (p < 0.05) but not with clinical severity.
Half the patients reported systemic reactions to peach. Peach allergy appeared predominantly mediated by Pru p 3 but some patients were sensitized to Pru p 4. Applying a 0.10 kU(A)/l cutoff level, the diagnostic value of combining the 3 recombinant allergens was noteworthy, with 100% sensitivity and 90% specificity.
IgE-reactive proteins in raspberry (Rubus ideaus L.) were identified using PCR, RT-PCR, 2-DE and MS/MS peptide sequencing. Specific polyclonal antibodies and patient sera were used in Western blotting to identify crossreactive epitopes. Initially, two potential allergens Rub i 1 and Rub i 3 were detected using PCR, showing high sequence identity to proteins in Rosaceous species like Mal d 1 and Mal d 3 from apple, Pru av 1 and Pru av 3 from cherry and Pru p 1 and Pru p 3 from peach. Furthermore, de novo identified peptides of a protein band at about 30 kDa reacting with most of the patient sera tested (> 80%) revealed a high sequence homology with class III chitinases. Raspberry chitinase, when subjected to glycoproteomic analysis, showed typical complex plant-type N-glycans with a core alpha1,3 fucose and a beta1,2 xylose at least at one position, indicating the presence of crossreacting carbohydrate determinants (CCDs). Finally, MS/MS analysis revealed an IgE-reactive raspberry cyclophilin, homologous to Bet v 7. Results obtained suggest that the consumption of raspberries might be responsible for adverse reactions in sensitised individuals.
To summarize recent findings on non-specific lipid transfer proteins in food allergy, with a specific focus on the localization, stability and route of sensitization.
Plant non-specific lipid transfer proteins are major food allergens, especially in the Mediterranean area. They have been identified as allergens in a number of foods and the list grows ever longer. As non-specific lipid transfer proteins are considered to be "true" food allergens that sensitize directly via the gastrointestinal tract their stability during food processing and gastric digestion has been studied in more detail. In addition, several groups have tried to determine the sensitization patterns of lipid transfer protein-reactive patients, to determine and possibly clarify the observed geographical differences in sensitization. Different sensitization routes (via the respiratory tract or even transdermally) have been suggested.
As the structure and molecular properties of non-specific lipid transfer proteins are resolved and more purified non-specific lipid transfer proteins become available for diagnostic purposes, detailed studies on the sensitization pattern and route are becoming feasible. Continuing studies on the pattern of lipid transfer protein sensitization will give more insight into the development and possible treatment of lipid transfer protein-related food allergy.
Hazelnut allergy in birch pollen-exposed areas is usually due to cross-reactivity (Cor a 1 and 2) and is usually mild in nature (oral allergy). In areas without birches, severe reactions are more prevalent and linked to sensitization to the lipid transfer protein (LTP) Cor a 8.
We sought to investigate whether sensitization to LTP plays a role in more severe (objective) hazelnut-induced symptoms in children from a birch-endemic area.
Sensitization to Cor a 8, Cor a 2, Cor a 1, and Bet v 1 was determined by means of RASTs and immunoblotting in hazelnut-sensitized children with (n = 8) and without (n = 18) objective reactions during double-blind, placebo-controlled food challenges. Additionally, samples from 191 hazelnut-sensitized nonchallenged children were analyzed.
Children with objective reactions during double-blind, placebo-controlled food challenge had higher IgE titers to hazelnut (P < .001) and recognized more allergens on immunoblotting (P = .001) than those without such reactions. All children with objective symptoms were sensitized to Cor a 8 (0.51-23.3 IU/mL) compared with only 1 child without objective reactions (0.90 IU/mL). In a multivariate analysis only IgE against Cor a 8 remained as an independent risk factor (undefined odds ratio; P < .0001). In the group of nonchallenged children (n = 191), the prevalence of LTP sensitization was greater than 30%. Unexpectedly, sensitization to Cor a 1 was observed in children not sensitized to Bet v 1.
Sensitization to hazelnut LTP is a risk factor for objective symptoms in children from a birch-endemic area.
Due to unclear reasons, allergy to lipid transfer protein (LTP) is frequent in Mediterranean countries but rare in Northern Europe.
We report a paradigmatic case of primarily airborne sensitization to LTP that might explain the geographical distribution of this type of food allergy.
A 21-year-old woman began having severe perennial rhinitis 6 months after she started working in a wholesale fruit storehouse in Southern Italy where large amounts of fruits, including peaches, were handled; symptoms subsided when she left the workplace for >5 days and relapsed as soon as she was back at work. Later on, she developed severe food allergies to peach, hazelnut, peanut, apricot, plum and tomato. The patient underwent a nasal challenge with peach peel extract, and IgE reactivity was assessed by immunoblot analysis.
In vivo and in vitro analyses showed sensitivity to LTP. The nasal challenge with peach peel extract (6 microg protein) induced acute, severe respiratory symptoms. On immunoblot with peach peel extract patient's serum reacted uniquely against LTP, as demonstrated by inhibition assays with the recombinant peach protein.
LTP may induce sensitization via the respiratory tract due to inhalation of air-dispersed food particles, and this may precede the onset of food allergy. If this way of sensitization were effective in the majority of LTP allergic patients (e.g. by exposure to peaches showing intact fuzz in areas where peaches are grown and directly sold on the market) our findings could explain the strange geographical distribution of this type of food allergy.
Several cross-reacting proteins have been identified as responsible of the co-occurrence of pollinosis and plant-derived food allergy. This association has been mainly described in the birch-apple syndrome but other pollens such as Olea europaea and other fruits may also contain homologous proteins.
To evaluate the associations between sensitization to allergens of Olea europaea pollen and confirmed plant-derived food allergy, in addition to investigate if any pattern of clinical hypersensitivity of food allergy reaction (oral allergy syndrome (OAS) or anaphylaxis) and/or any fresh fruit or nut allergy, are associated to one or several Olea pollen allergen(s).
One-hundred and thirty-four consecutive patients diagnosed with pollinosis by Olea were studied. Of these patients only 40, reported adverse reaction to plant-derived food. Twenty-one (group A) were classified as OAS and 19 (group B) as anaphylaxis. Skin-tests with six Olea pollen allergens and several groups of fruits, were performed. Double-blind placebo-controlled food challenge (DBPCFC), confirmed the diagnostics of food allergy with the exception of patients who suffered previous anaphylactic reaction.
All patients, showed a positive skin prick test (SPT), against one or more of Olea europaea allergens. Sensitization to Ole e 7, was more frequent (P = 0.02) in patients from group B. A total of 84 DBPCFC were performed with 44% positive results. Challenge confirmed at least the 50% of positive SPT in any case (peach: 68.42%; pear: 50%; melon: 71.42% and kiwi: 53.84%). In patients from group B, significant association with O. europaea pollen allergens were found between positive SPT to Rosaceae fruits and Ole e 3 (P = 0.045) and Ole e 7 (P = 0.03); Cucurbitaceae and Ole e 7 (P = 0.03) and Actinidiaceae with Ole e 3 (P = 0.04).
The results of this study, establish a new spectrum of associations between pollens and plant-derived foods: sensitization to olive profilin (Ole e 2) is not more frequent in OAS patients. Patients with anaphylactic reaction after eating fruit are also sensitized to Ole e 7, a LTP present in Olea pollen, and suffer pollinic symptoms. Finally a polcalcin (Ole e 3) could be also associated to Olea pollen respiratory and food allergy.
The true prevalence of food allergy as an IgE mediated reaction is still under discussion. Using apple as a model allergen source a multidisciplinary consortium worked together at developing various strategies for reducing the incidence of fruit allergies in an EC-funded project. Patient allergen profiles were established using in vitro and in vivo tests with respect to geographic area and mild or severe symptoms. Apple allergens (Mal d 1-Mal d 4) were characterised, variants identified, cloned and sequenced. These individual allergens were used to increase the sensitivity and specificity of diagnosis. Furthermore, they provided better prognosis of disease severity. RT-PCR and ELISA were developed for determining the allergen specific mRNA and expressed allergenic protein in a large number of apple cultivars. Similarly, changes in allergen characteristics from harvest through storage to processing and the impact of agronomic practices were investigated. Allergen genes were mapped on a molecular linkage map of apple. The biological function of Mal d 1 was studied using the RNA interference strategy. Finally, consumer attitudes in Northern, Central and Southern Europe were gauged on the acceptability of low allergen cultivars or a GMO and its impact on product quality.