Fabacées et LTP

BACKGROUND: Rosaceae fruit allergy is frequently associated with birch pollinosis in Central and Northern Europe and with grass pollen allergy in Central Spain. The main cross-reactive structures involved for birch pollinosis are Bet v 1 and profilin, and for grass pollinosis they are profilin and carbohydrate determinants. Rosaceae fruit allergy can occasionally be observed in patients without pollinosis . OBJECTIVE: We investigated the clinical presentation and the allergens involved in allergy to Rosaceae fruit without pollinosis . METHODS: Eleven patients from Central Spain allergic to apples, peaches, and/or pears but not to pollens were compared with 22 control subjects with combined grass pollen and fruit allergy. Skin prick tests and RASTs to apple, peach, and pear were performed. Cross-allergenicity was studied by RAST inhibition. Bet v 1 was tested with an indirect RAST, and profilin was tested in skin prick tests, histamine release, and RAST . RESULTS: Rosaceae fruit allergy without pollinosis is severe with 82% of patients reporting systemic symptoms, mainly anaphylaxis (73%), whereas oral symptoms are less frequent (64%). Anaphylactic shock was observed in 36% of patients. The fruit allergens involved showed cross-reactivity among Rosaceae species but were not related to profilin or Bet v 1. Ninety-one percent of patients with combined grass pollinosis and fruit allergy reported oral allergy, 45% reported systemic symptoms, 18% reported anaphylaxis, and 9% reported anaphylactic shock . CONCLUSION: Allergy to Rosaceae fruits in patients without a related pollen allergy is a severe clinical entity. Profilin- and Bet v 1-related structures are not involved in Rosaceae fruit allergy without pollinosis.

Foods from the Rosaceae botanical family have been increasingly reported as causes of allergic reaction. Patients frequently have positive skin tests or radioallergosorbent test results for multiple members of this botanical family. OBJECTIVE: Our purpose was to investigate the clinical cross-reactivity assessed by double-blind, placebo-controlled food challenge (DBPCFC) of Rosaceae foods (apricot, almond, plum, strawberry, apple, peach, and pear). METHODS: Thirty-four consecutive adult patients complaining of adverse reactions to Rosaceae were included in the study. Skin prick tests and CAP System (FEIA) were performed with Rosaceae foods in all patients. Clinical reactivity to Rosaceae was systematically evaluated by open food challenges (OFCs), unless there was a convincing history of a recent severe anaphylaxis. Positive reactions on OFCs were subsequently evaluated by DBPCFCs. RESULTS: Twenty-six and 24 patients had positive skin prick tests and CAP FEIA with Rosaceae, respectively; from these 88% and 100% had positive tests with >/=2. No evidence of clinical reactivity was found in 66% percent of positive skin prick tests and 63% of positive specific IgE determinations to fruits. A total of 226 food challenges (including OFC and DBPCFC) were performed in the 28 patients with positive skin prick tests or CAP System FEIA. Of 182 initial OFCs carried out, 26 (14%) reactions were confirmed by DBPCFCs. Overall, 40 reactions were considered positive in 22 patients with positive skin tests or CAP FEIA. Thirty-eight reactions had been previously reported, the remaining two were detected by systematic challenges. Most reactions were caused by peach (22 patients), apple (6), and apricot (5). Ten patients (46%) were clinically allergic to peach and other Rosaceae. CONCLUSION: Positive skin test and CAP System FEIA should not be taken as the only guide for multi-species dietary restrictions. Nevertheless, the potential clinical allergy to other Rosaceae should not be neglected. If the reported reaction is confirmed, current tolerance to other Rosaceae should be precisely established unless there has been ingestion without symptoms after the reaction.

BACKGROUND: Lipid transfer proteins (LTP) are highly conserved and widely distributed throughout the plant kingdom. Recent studies demonstrated immunological cross-reactivity between LTP from many botanically unrelated fruits and vegetables and concluded that LTP are pan-allergens. This study aimed to evaluate the clinical relevance of such cross-reactivity in a group of subjects monosensitized to LTP . METHODS: Twenty LTP-hypersensitive patients were selected from a population of about 600 subjects with history of Rosaceae allergy by means of: 1) negative skin prick test (SPT) with a commercial birch pollen extract; 2) positive SPT with a commercial plum extract, rich in LTP but virtually lacking both Bet v 1-like proteins and profilin; 3) in-vitro IgE reactivity to the 9-10 kDa fraction of peach peel or immunoblot with peach peel showing a single band at 10 kDa; and 4) total inhibition of reactivity to whole peach extract (containing Bet v 1-related allergen, profilin, and LTP) by purified peach LTP on enzyme-linked immunoassay (ELISA). Allergy to foods other than Rosaceae was ascertained by careful interview and analysis of medical recordings. SPT with a large series of plant-derived foods were carried out as well. The cross reactivity between LTPs from botanically unrelated plant-derived foods was assessed by ELISA inhibition tests using walnut and peanut extracts as substrate, and peach LTP as inhibitor . RESULTS: All patients reported allergic reactions after the ingestion of at least one from a large number of vegetable foods other than Rosaceae, and in several cases clinical reactions were very severe (anaphylaxis, asthma, urticaria/angioedema). Nuts and peanuts were the most frequently reported causes of allergic reactions (80% and 40% of patients, respectively). All patients showed positive SPT to several non-Rosaceae food extracts. SPT with nuts, peanut, legumes, celery, rice, and corn were positive in the majority of patients. In ELISA inhibition studies, absorption of sera with peach LTP caused complete inhibition of IgE reactivity to walnut and peanut in all cases . CONCLUSION: LTP is a clinically relevant pan-allergen. Most Rosaceae-allergic, LTP-hypersensitive patients experience adverse reactions after ingestion of botanically unrelated plant-derived foods as well. In view of the high prevalence and severity of the allergic reactions induced, hazelnut, walnut, and peanut should be regarded as potentially hazardous for these patients.

BACKGROUND: Cor a 1.04 has been identified as the major hazelnut allergen in 65 European patients with positive double-blind, placebo-controlled food challenge results to hazelnut. Recently, the 11S globulin Cor a 9 was shown to be a pollen-independent hazelnut allergen in the United States, whereas preliminary data suggest the lipid transfer protein (LTP) as an important birch pollen-unrelated hazelnut allergen in Europe . OBJECTIVE: We sought to recruit a group of European patients allergic to hazelnut without birch pollen allergy and to identify and clone the major food allergen(s) in this study population . METHODS: We recruited 26 such Spanish patients, including 10 patients with anaphylaxis. IgE immunoblotting was performed with hazelnut extract. Hazelnut LTP Cor a 8 was cloned by using a PCR strategy, purified, and subjected to IgE immunoblotting. Recombinant Cor a 8, rCor a 1.0401, and rCor a 2 (profilin) were further investigated by means of enzyme allergosorbent test. Immunoblot inhibition experiments were used to compare the immunologic properties of natural and recombinant LTP . RESULTS: A 9-kd major allergen was identified in hazelnut extract. Cloning, sequencing, heterologous expression, and inhibition experiments identified it as an LTP. The prevalence of specific IgE antibody reactivity to LTP was 62% in hazelnut extract and 77% when recombinant LTP was tested by means of immunoblotting. IgE immunoblot inhibition with hazelnut extract showed that natural Cor a 8 and rCor a 8 shared identical epitopes. Only one patient had positive reactivity to Cor a 1.04, and no patients had positive reactivity to Cor a 2. Two sera bound to high-molecular-weight allergens. The LTP was denominated as Cor a 8 and submitted to the allergen database of the World Health Organization/International Union of Immunological Societies Allergen Nomenclature Subcommittee . CONCLUSIONS: Cor a 8 is a relevant allergen for a majority of Spanish patients with hazelnut allergy that can cause severe allergic reactions.

BACKGROUND: Lipid transfer protein (LTP), the major allergen in Rosaceae in geographic areas where the prevalence of birch pollen allergy is low, is a widely cross-reacting pan-allergen, but the pattern of cross-reactivity to plant-derived foods botanically unrelated to Rosaceae shows much variability. OBJECTIVE: To examine the relationship between peach LTP specific IgE levels and cross-reactivity to several non-Rosaceae, plant-derived foods. METHODS: IgE specific for peach LTP was measured by enzyme-linked immunosorbent assay in serum samples from 40 patients with Rosaceae allergy monosensitized to LTP. Patients were considered monosensitized to this protein in the absence of sensitization to other cross-reacting, plant-derived foods as shown by negative skin prick test (SPT) results with both birch and mugwort pollen. SPTs with commercial extracts of walnut, hazelnut, peanut, celery, maize, rice, tomato, orange, and onion were performed to detect possible immunologic cross-reactivity to these foods. RESULTS: Patients with negative SPT results with non-Rosaceae foods showed significantly lower levels of IgE to peach LTP than patients showing skin reactivity to one or more non-Rosaceae foods (P < .001). A significant difference in specific IgE to peach LTP between patients with positive or negative SPT results was observed with each individual food (P < .001 in all cases). The level of IgE to peach LTP was strongly related to the number of positive SPT results with non-Rosaceae foods (r = 0.78; P < .001). Increasing levels of IgE to peach LTP were associated with skin reactivity to nuts (29/40 [72%]), peanut (27/40 [67%]), maize (16/39 [41%]), rice (14/39 [36%]), onion (13/37 [35%]), orange (9/32 [28%]), celery (11/40 [27%]), and tomato (8/39 [20%]). CONCLUSIONS: This study suggests that all allergenic determinants in LTP from vegetable foods other than peach cross-react with peach LTP determinants, whereas only some peach LTP epitopes cross-react with allergenic determinants on botanically unrelated, plant-derived foods. The high levels of IgE to peach LTP seem to reflect the presence of IgE targeting common allergenic determinants of LTP, causing cross-reactivity to botanically unrelated, vegetable foods. In LTP-allergic patients, increasing levels of IgE to peach LTP are paralleled by an increasing number of foods other than Rosaceae positive on SPT that cause clinical symptoms.

Reports of immunoglobulin E (IgE)-mediated allergic reactions to grapes and wine are limited in the literature. Nevertheless, grapes are widely grown and consumed in Mediterranean countries. The object of this prospective study was to present clinical features, in vivo and in vitro allergy testing, and human leukocyte antigen (HLA) serotyping in patients with recurring reactions to grapes and grape products. Eleven unrelated Greek patients, six men and five women (aged 16-44 years; mean, 26.9 years) were enrolled based on a documented history of IgE-mediated reactions to grapes, wine, or other grape products. Their evaluation included full history, reaction severity, clinical examination, skin-prick tests with food allergens and molds, serum IgE, specific IgEs to the same allergen battery, and HLA typing. Patients reported 35 grape-induced anaphylaxis episodes ranging from moderate (more than one system involved but not prominent respiratory or cardiovascular symptoms; 45.5%) to severe (serious respiratory obstruction and/or hypotension and loss of consciousness; 54.5%). A causative agent was identified: wine, 10/35 (28.6%); red grapes, 9/35 (25.7%); stuffed vine leaves, 8/35 (22.9%); raisins, 3/35 (8.6%); white grapes, 2/35 (5.7%); wine vinegar, 2/35 (5. 7%); and grape juice, 1/35 (2.9%). Other foods that induced anaphylaxis were apples (54.5%), cherries (18.6%), peaches (18.6%), and bananas (9.3%). Specific IgE values were in accordance with skin-prick tests reactivity. Concerning HLA typing, 9/11 possessed HLA-DR11(5) and -DQ7(3) and the remaining two possessed HLA-DR17(3) and -DQ2 antigens. Grapes, wine and other grape products might cause serious allergic reactions in sensitized individuals. The cosensitization and reaction incidence to other fruit allergens could be a basis for further investigation of panallergens of fruits. HLA class II antigens may contribute in genetic predisposition to these allergic reactions.

The grape is widely produced and consumed in the Mediterranean area. The object of this prospective study was to present in detail the clinical features of patients with documented immunoglobulin E (IgE)-mediated reactions to grapes or its products as well as the existing cosensitizations in other food allergens among this population. Sixty-one patients (27 male patients and 34 female patients), aged 14-52 years (mean, 28.8 years) with a documented history of IgE-mediated reactions to grapes or its products (wine, juice, and wine vinegar) were included in this study. In each patient, full allergological data, clinical examination, and specific in vivo (skin-prick tests and prick-to-prick) and in vitro (grape-specific IgE) evaluations were recorded. The diagnostic procedure was extended in other food allergens and molds for exclusion of fruit surface contamination. Thirty-seven of 61 (60.7%) patients had a positive personal history and 24/61 (39.3%) patients had a family history of atopy. Patients reported 3.1 episodes/patient (range, 1-15 episodes) after consumption of grapes or its product. Forty-seven of 61 (77%) patients had presented oral allergy syndrome after eating grapes before the first reported reaction. The mean time for the onset of symptoms was 42 minutes (4-160 minutes). Forty-four of 61 (72.1%) patients reported more than one reaction. The observed prevalence of symptomatology according to the system involved was determined: skin, 57/61(93.4%) patients; respiratory, 46/61(75.4%) patients; cardiovascular, 27/61 (44.3%) patients; and gastrointestinal, 24/61(39.3%) patients. The main cosensitizations were identified (skin-prick tests): apples, 81.9%; peaches, 70.5%; cherries, 47.5%; strawberries, 32.8%; peanuts, 49.2%; walnuts, 42.6%; hazelnuts, 31.1%; almonds, 26.2%; and pistachios, 29.5%. The grape and its products may be the offending agent of IgE-mediated reactions in sensitized individuals. The high prevalence of concomitant reactivity to other fruits elicits the interest of clinical relevance of these findings among the grape-allergic population.

BACKGROUND: Grape allergy is considered rare; grape lipid transfer protein (LTP; Vit v 1), an endochitinase and a thaumatin-like protein (TLP) have been reported as grape allergens. A considerable number of patients have referred to our department for severe reactions to grapes, and several IgE binding proteins were detected . OBJECTIVES: The aim of this study was to identify and characterise the allergens involved in severe allergic reactions to grapes and describe the population in which they occur . METHODS: Patients with reported severe allergic reactions to grapes (n = 37) are described. Grape allergens were purified/fractionated by a combination of chromatographic techniques, identified by proteomic analysis and biochemically characterised. Immunoreactivity was assessed by blot (inhibitions) and RAST (inhibitions), and skin prick tests were performed with the isolated allergens . RESULTS: All subjects were polyallergic, sensitised and reactive to several additional foods and pollen. All patients were sensitised to grape LTP. A 28-kDa expansin, a 37.5-kDa polygalacturonase-inhibiting protein, a 39-kDa beta-1,3-glucanase and a 60-kDa protein were identified as minor grape allergens. Endochitinase and TLP did not play a role. Inhibition experiments revealed the possible cross-reactive role of LTP for clinical sensitivities to other LTP-containing plant foods, but also the involvement of cross-reactive carbohydrate determinants of minor allergens in IgE cross-reactivity . CONCLUSIONS: LTP is the major grape allergen, while additional minor allergens may contribute to clinical reactivity. Severe grape allergy presents in atopic patients who frequently react to other LTP-containing, plant-derived foods. The 'LTP syndrome' is the appropriate term to describe this condition.

BACKGROUND: Lipid transfer protein (LTP) is a widely cross-reacting plant pan-allergen. Adverse reactions to Rosaceae, tree nuts, peanut, beer, maize, mustard, asparagus, grapes, mulberry, cabbage, dates, orange, fig, kiwi, lupine, fennel, celery, tomato, eggplant, lettuce, chestnut and pineapple have been recorded . OBJECTIVE: To detect vegetable foods to be regarded as safe for LTP-allergic patients . METHODS: Tolerance/intolerance to a large spectrum of vegetable foods other than Rosaceae, tree nuts and peanut was assessed by interview in 49 subjects monosensitized to LTP and in three distinct groups of controls monosensitized to Bet v 1 (n = 24) or Bet v 2 (n = 18), or sensitized to both LTP and birch pollen (n = 16), all with a history of vegetable food allergy. Patients and controls underwent skin prick test (SPT) with a large spectrum of vegetable foods. The absence of IgE reactivity to foods that were negative in both clinical history and SPT was confirmed by immunoblot analysis and their clinical tolerance was finally assessed by open oral challenge (50 g per food) . RESULTS: All patients reported tolerance and showed negative SPT to carrot, potato, banana and melon; these foods scored positive in SPT and elicited clinical symptoms in a significant proportion of patients from all three control groups. All patients tolerated these four foods on oral challenge. Immunoblot analysis confirmed the lack of IgE reactivity to these foods by LTP-allergic patients . CONCLUSION: Carrot, potato, banana and melon seem safe for LTP-allergic patients. This finding may be helpful for a better management of allergy to LTP.

RATIONALE: The presence of an LTP in peanut has been hypothesized but never confirmed. The aim was to identify LTP in peanut extract and characterize its physicochemical and immunological properties. METHODS: Identification of peanut LTP with cross-reacting rabbit anti- Cor a 8 antiserum, sera from peach and peanut-allergic patients‚ sera, and N-terminal sequencing. RESULTS: Peanut LTP was identified in an acidic extract of peanut meal at 8 kDa by immunoblotting and by N-terminal sequencing. The IgE reactivity of two cloned and expressed isoallergens was demonstrated with sera from peach and peanut-allergic patients by immunoblotting. The immunoblot analysis with patients‚ sera showed IgE-reactivity to natural LTP in 68% (n = 25) of patients allergic to peanut and peach (Pru p 3 positive) and 24% (n = 17) of peach-allergic patients (Pru p 3 positive), which are asymptomatic to peanut. Only a weak LTP reactivity was detectable in 29% (n = 24) of patients with peanut allergy (Pru p 3 negative). CONCLUSIONS: For the first time peanut LTP is described as a novel allergen with immunological and molecular biological methods. The N-terminal sequence data allowed cloning and production of recombinant LTP from peanut. Based on clinical data we suggest that the main sensitization of peanut allergic patients to peanut LTP is caused by cross reactivity to Pru p 3, but peanut LTP as sensitizing allergen cannot be excluded. The clinical relevance of peanut LTP remains an open question until peanut-allergic patients are challenged with the full panel of peanut allergens.

BACKGROUND: 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 . OBJECTIVE: 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 . METHODS: 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 . RESULTS: 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 . CONCLUSION: Sensitization to hazelnut LTP is a risk factor for objective symptoms in children from a birch-endemic area.

A minority of patients with oral allergy syndrome (OAS) induced by Rosaceae or nuts are positive on skin prick tests with commercial food extracts. This suggests reactivity against distinct stable allergens. OBJECTIVES: (1) To define the prevalence of subjects positive on skin prick tests with commercial extracts among patients with OAS caused by Rosaceae and/or nuts and (2) To investigate whether commercial extracts-positive subjects show some peculiar clinical feature and may represent a specific subset with food allergy. METHODS: Skin prick tests were carried out with a large panel of commercial extracts of airborne allergens (Allergopharma) and of vegetable foods (Dome/Hollister-Stier) in 298 adults with OAS caused by Rosaceae (n = 237) and or nuts (n = 161), positive on skin prick tests with fresh offending foods. RESULTS: 25/237 (11%) patients were positive on prick tests with commercial plum extract. This subgroup showed a higher incidence of systemic symptoms (64% versus 6%; P < .001) and a lower incidence of birch pollen allergy (12% versus 99%; P < .001) than commercial extract-negative patients; moreover, 36% versus 0%, respectively, did not have respiratory allergy (P < .001). Apple and peach were the main offending foods among commercial extract-negative and commercial extract-positive patients, respectively (87% versus 44% for apple, P < .001; and 52% versus 88% for peach, P < .005). Eight of one hundred sixty-one (5%) nuts-sensitive patients were positive on prick test with commercial walnut extract. This subgroup showed a higher proportion of patients who experienced systemic symptoms (63% versus 6%, P < .001), a lower prevalence of birch pollen allergy (13% versus 97%, P < .001), and a higher prevalence of grass pollen allergy (88% versus 41%, P < .05) than commercial extract-negative subjects. Further, reactivity against commercial walnut extract was associated with skin reactivity against commercial extracts of peanut (88% versus 37%, P < .005), tomato (75% versus 5%, P < .001), and plum (63% versus 8%, P < .001), and inversely related with skin reactivity against fresh apple (P < .001). In most cases, high levels of IgE specific for peach, apple, and hazelnut were associated with peanut reactivity rather than with clinical sensitivity to specific foods. In a preliminary investigation, most commercial extract-positive patients reacted against a 10-kDa protein characterized as a lipid transfer protein (LTP). CONCLUSIONS: Skin prick tests with commercial extracts of plum and walnut may be usefully employed to detect patients with OAS reacting against stable allergens. The high prevalence of systemic symptoms in these patients suggests that allergens' stability is associated with a higher resistance to the gastrointestinal environment and strongly influences the clinical expression of vegetable food allergy. At least some stable allergens, namely lipid transfer protein might be shared by botanically unrelated fruits such as nuts, peanuts, legumes, tomato, and Prunoideae.