Le raisin (et ses dérivés)

[1] - Rodriguez A, Matheu V, Trujillo MJ, Martinez MI, Baeza ML, Barranco R, et al. Grape allergy in paediatric population. Allergy 2004;59:364

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[2] - Pastorello EA, Farioli L, Pravettoni V, Ortolani C, Fortunato D, Giuffrida G, et al. Identification of grape and wine allergens as an endochitinase 4, a lipid-transfer protein, and a thaumatin. J Allergy Clin Immunol 2003;111:350-359

BACKGROUND: Few allergic reactions to grape are reported in the literature. In some cases an association with peach and cherry allergy was observed. No IgE-mediated reactions to wine have been described, and no grape major allergens have yet been identified . OBJECTIVE: We describe several severe reactions to grape or wine. We characterized the grape major allergens and tried to identify the allergen in wine . METHODS: We collected documented histories of allergic reactions to grape and wine. Grape allergens were identified by means of SDS-PAGE and immunoblotting and purified by means of HPLC. Using amino acid sequencing and mass spectrometry, we identified the family of proteins to which the allergens belong. Cross-reactivity with peach and cherry was evaluated by means of cross-wise inhibition experiments . RESULTS: Eleven patients with reactions to grape and 3 with anaphylactic reactions to wine were recruited. The major allergens were an endochitinase 4A and a lipid-transfer protein (LTP) that was homologous to and cross-reactive with peach LTP. A 24-kd protein homologous to the cherry thaumatin-like allergen was a minor allergen. Endochitinase 4A is very likely the allergen in vino novello and in vino Fragolino . CONCLUSIONS: Grape and wine might cause severe allergic reactions in sensitive patients. The major allergens of grape are endochitinase 4A, which is also the allergen of wine, and an LTP cross-reacting with the peach major allergen.

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[3] - Kalogeromitros DC, Makris MP, Gregoriou SG, Mousatou VG, Lyris NG, Tarassi KE, et al. Grape anaphylaxis: a study of 11 adult onset cases. Allergy Asthma Proc 2005;26:53-58

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.

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[4] - Kalogeromitros DC, Makris MP, Gregoriou SG, Katoulis AC, Straurianeas NG. Sensitization to other foods in subjects with reported allergy to grapes. Allergy Asthma Proc 2006;27:68-71

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.

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[5] - Vassilopoulou E, Zuidmeer L, Akkerdaas J, Tassios I, Rigby NR, Mills ENC, et al. Severe Immediate Allergic Reactions to Grapes: Part of a Lipid Transfer Protein-Associated Clinical Syndrome. Int Arch Allergy Immunol 2007;143:92-102

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.

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[6] - Pétrus M, Malandain H. Allergie alimentaire au raisin. Une nouvelle observation chez un enfant de 4 ans. Rev Fr Allergol Immunol Clin 2002;42:806-809

L'allergie au raison est rare : trois observations pédiatriques sont connues et une vingtaine d'observations chez l'adulte. Les motifs de consultation sont, le plus souvent, un syndrome oral ; mais, des manifestations plus graves sont possibles : asthme, anaphylaxie à l'effort, choc anaphylactique. Les auteurs rapportent l'observation d'un garçon de 4 ans, présentant une allergie au raisin, dont les symptômes cliniques sont limités à un syndrome oral. Le diagnostic est affirmé par les tests cutanés au raisin natif, le test labial et le dosage des IgE sériques spécifiques. Cette allergie s'intègre dans le cadre d'un syndrome d'allergies multiples : acariens, pollens de graminées, blanc d'uf, poisson, noix de coco, kiwi, amande, latex. Les relations moléculaires, pouvant expliquer cette association d'allergies, sont discutées.

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[7] - Schäd SG, Trcka J, Vieths S, Scheurer S, Conti A, Trautman A. Wine Anaphylaxis in a German Patient: IgE-Mediated Allergy against a Lipid Transfer Protein of Grapes. Int Arch Allergy Immunol 2005;136:159-164

BACKGROUND: IgE-mediated allergy to grapes has very rarely been reported in patients from the Mediterranean area. Recently, endochitinase 4 and a lipid transfer protein (LTP) have been identified as major allergens in grape-allergic patients who do not have an associated pollinosis. The purpose of this case study was to identify the allergens responsible for severe anaphylactic reactions after consumption of wine, fresh grapes and raisins in a German patient . METHODS: Prick-to-prick tests and the basophil activation test (BAT) were performed to confirm allergy. Specific IgE was further analyzed by immunoblotting and inhibition tests for the determination of crossreactivity. The IgE-binding protein was subjected to N-terminal microsequencing . RESULTS: Prick-to-prick tests were positive to fresh and cooked white and blue grapes, to raisins, to white and red wine, and to grape extract. Specific IgE against grapes (f259) was 2.43 kU/l (class 2). The BAT showed specific IgE-mediated activation of basophils after stimulation with grape extract. IgE binding to a 15-kDa protein was completely inhibited by pre-incubation with recombinant cherry LTP Pru av 3. N-terminal sequencing identified this 15-kDa protein as grape LTP Vit v 1 . CONCLUSION: Our data show that sensitization to LTP can occur outside the Mediterranean area causing severe fruit allergy without association to pollinosis.

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[8] - Gebhardt C, Vieths S, Gubesch M, Averbeck M, Simon JC, Treudler R. 10 kDa lipid transfer protein: the main allergenic structure in a German patient with anaphylaxis to blueberry. Allergy 2009;64:498-499

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[9] - Vaswani SK, Chang BW, Carey RN, Hamilton RG. Adult onset grape hypersensitivity causing life threatening anaphylaxis. Ann Allergy Asthma Immunol 1999;83:25-26

BACKGROUND: Adverse reactions to foods are encountered much less frequently in adults than in the children. Adult onset hypersensitivity to grapes has not been previously reported. OBJECTIVE: Evaluation of a case of anaphylaxis that occurred as a result of the consumption of white grapes (Vitis vinifera). METHODS AND RESULTS: A 28-year-old woman experienced generalized urticaria, facial/oropharyngeal angioedema, and dizziness after eating a bunch of white grapes. She was treated in an emergency room for anaphylaxis. Previously, she had experienced two similar episodes after eating white grapes. The grape prick skin tests were strongly positive forming a pseudopod type reaction. The total serum IgE was 1918 ng/mL. The grape-specific serum IgE was weakly positive by the modified RAST and negative in the Pharmacia-Upjohn Cap System. CONCLUSION: Hypersensitivity to a commonly consumed fruit such as grapes can develop late in life causing a near-fatal anaphylaxis.

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[10] - Vaswani SK, Chang BW, Carey RN, Hamilton RG. Adult onset grape hypersensitivity causing life threatening anaphylaxis. Ann Allergy Asthma Immunol 1999;83:25-26

BACKGROUND: Adverse reactions to foods are encountered much less frequently in adults than in the children. Adult onset hypersensitivity to grapes has not been previously reported. OBJECTIVE: Evaluation of a case of anaphylaxis that occurred as a result of the consumption of white grapes (Vitis vinifera). METHODS AND RESULTS: A 28-year-old woman experienced generalized urticaria, facial/oropharyngeal angioedema, and dizziness after eating a bunch of white grapes. She was treated in an emergency room for anaphylaxis. Previously, she had experienced two similar episodes after eating white grapes. The grape prick skin tests were strongly positive forming a pseudopod type reaction. The total serum IgE was 1918 ng/mL. The grape-specific serum IgE was weakly positive by the modified RAST and negative in the Pharmacia-Upjohn Cap System. CONCLUSION: Hypersensitivity to a commonly consumed fruit such as grapes can develop late in life causing a near-fatal anaphylaxis.

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[11] - Rachid RA, Broff M, Twarog FJ. Anaphylaxis From Grapes in a Pediatric Patient. J Allergy Clin Immunol 2001;107(2 part 2):S271

Allergic reactions to grapes have rarely been reported. We report an eight year old patient with symptoms consistent with anaphylaxis after grape ingestion. KR is an 8 year old boy with atopic dermatitis and attention deficit disoder , who had few months prior to his presentation to our clinic an upper respiratory infection with runny nose and low grade fever. He was given some apple juice by his mother, which was well tolerated, followed by red grapes. Immediatly after the grapes‚ ingestion, he had ocular swelling, then developed hoarseness of the voice followed by appearance of hives all over the body and finally started complaining of difficulty to breath. He was immediatly taken to the Emergency Room in a local hospital, where he was given epinephrine injections and was kept overnight for observation. He was prescribed an Epipen Jr . Mom reports that at the age of seven years, he developed a rash following the ingestion of peanut butter and grape jelly sandwich. Of note, there is no history of nuts or peanuts ingestion, latex exposure, medication intake (except for Ritalin , which is well tolerated) prior to his anaphylaxis episode. His physical exam in our clinic was positive for eczematous lesions over the popliteal areas. Prick skin test with commercial extract was positive for grape ( with a wheal of 15 mm), peanut, walnut, brazil nut, almond , hazel nut and cat with a negative saline control. Five control individuals were negative for the grape prick test. Our patient presented with symptoms of anaphylaxis following grape ingestion and had a positive prick test consistent with a type I sensitivity to grape. Grape anaphylaxis is exceedingly rare, and have been reported in only few patients in Europe and Japan. This is the first US pediatric patient reported in the literature with grape anaphylaxis.

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[12] - Rodriguez A, Matheu V, Trujillo MJ, Martinez MI, Baeza ML, Barranco R, et al. Grape allergy in paediatric population. Allergy 2004;59:364

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[13] - Guinnepain MT, Rassemont R, Laurent J. Le raisin est aussi un trophallergène. Rev Fr Allergol Immunol Clin 1997;37:400

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[14] - Ben M'rad S, Dridi A, Doggui MH, Khouani H, Tritar F, Merai S, et al. L'allergie alimentaire à la pêche. Rev Fr Allergol Immunol Clin 2005;45:385-388

La pêche est un fruit répandu en région méditerranéenne. Il appartient à la famille des Rosacées qui comprend outre les pêches, les pommes, les cerises, les poires, les abricots, les framboises, les fraises, les noisettes et les amandes. Bien que la fréquence réelle de l'allergie à la pêche soit méconnue, cette dernière semble en augmentation. L'allergène majeur est une protéine de transfert lipidique très répandue dans le règne végétal et intervient dans la défense des plantes contre les agressions extérieures. Une allergie croisée avec les autres fruits de la famille des Rosacées et avec les pollens de bouleau et de graminées est fréquente. Nous faisons le point sur cette pathologie à travers l'étude de cinq observations de patients présentant une allergie alimentaire à la pêche ainsi qu'une revue de la littérature.

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[15] - Campina Costa S, Costa Silva I, Romeira A, Rosa S, Bartolomé Zavala B, Leria Pinto P. Grape allergy and coexisting sensitisations. Allergy 2008;63(suppl. 88):587

Background: Grape allergy is uncommon but a considerable number of allergic reactions to grape have been recently reported, particularly in the Mediterranean countries where it is widely consumed. We report two clinical cases of grape anaphylaxis. The first patient (1Pt) is a 19-year-old woman who suffered from anaphylactic reactions after grape, almond and pistachio ingestion and oral-allergy syndrome to peach and kiwi. The second patient (2Pt) is a 59-year-old woman who reported an anaphylactic reaction after grape ingestion and oral-allergy syndrome to walnuts and fig. Neither of them had symptoms with other grape products like wine or wine vinegar. Methods: Skin prick tests (SPT) were performed with extracts from almond, pistachio, walnut and hazelnut (Bial-Aristeguis). Prick-prick tests (PPT) were performed to grape, raisin, wine and wine vinegar. Specific IgE to grape, almond, pistachio, walnut and hazelnut were determined by EAST method. PPT and specific IgE to peach and kiwi were also performed for the 1Pt and PPT to fig was done for the 2Pt. Results: For the 1Pt: SPT were positive to almond, pistachio and hazelnut; PPT to grape, raisin, peach and kiwi were positive; serum specific IgE were positive against peach (2.99 kU/L), grape (0.9 kU/L), kiwi (1.1 kU/L), lipid transfer protein (LTP) from peach (3.2 kU/L) and negative (o 0.35 kU/L) against almond and pistachio. For the 2Pt: SPT were positive to walnut and hazelnut; PPT to grape, raisin, wine, wine vinegar and fig were positive; specific IgE to grape as well as to walnut and hazelnut were negative. Conclusion: We report two cases of severe IgE-mediated reactions to grape with coexisting sensitisation to other food allergens. The clinical relevance of the concomitant reactivity to other fruits points out the need to better investigate the pattern of crossreactivity in patients with grape allergy.

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[16] - Gebhardt C, Vieths S, Gubesch M, Averbeck M, Simon JC, Treudler R. 10 kDa lipid transfer protein: the main allergenic structure in a German patient with anaphylaxis to blueberry. Allergy 2009;64:498-499

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[17] - Sbornik M, Rakoski J, Mempel M, Ollert M, Ring J. IgE-mediated type-I-allergy against red wine and grapes. Allergy 2007;62:1339-1340

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[18] - Senna G, Mistrello G, Roncarolo D, Crivellaro M, Bonadonna P, Schiappoli M, et al. Exercise-induced anaphylaxis to grape. Allergy 2001;56:1235-1236

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[19] - Garcia-Robaina JC, de la Torre-Morin F, Sanchez-Machin I, Sanchez-Monge R, Barber D, Lombardero M. Anaphylaxis induced by exercise and wine. Allergy 2001;56:357-358

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[20] - Pastorello EA, Farioli L, Pravettoni V, Ortolani C, Fortunato D, Giuffrida G, et al. Identification of grape and wine allergens as an endochitinase 4, a lipid-transfer protein, and a thaumatin. J Allergy Clin Immunol 2003;111:350-359

BACKGROUND: Few allergic reactions to grape are reported in the literature. In some cases an association with peach and cherry allergy was observed. No IgE-mediated reactions to wine have been described, and no grape major allergens have yet been identified . OBJECTIVE: We describe several severe reactions to grape or wine. We characterized the grape major allergens and tried to identify the allergen in wine . METHODS: We collected documented histories of allergic reactions to grape and wine. Grape allergens were identified by means of SDS-PAGE and immunoblotting and purified by means of HPLC. Using amino acid sequencing and mass spectrometry, we identified the family of proteins to which the allergens belong. Cross-reactivity with peach and cherry was evaluated by means of cross-wise inhibition experiments . RESULTS: Eleven patients with reactions to grape and 3 with anaphylactic reactions to wine were recruited. The major allergens were an endochitinase 4A and a lipid-transfer protein (LTP) that was homologous to and cross-reactive with peach LTP. A 24-kd protein homologous to the cherry thaumatin-like allergen was a minor allergen. Endochitinase 4A is very likely the allergen in vino novello and in vino Fragolino . CONCLUSIONS: Grape and wine might cause severe allergic reactions in sensitive patients. The major allergens of grape are endochitinase 4A, which is also the allergen of wine, and an LTP cross-reacting with the peach major allergen.

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[21] - Ferreira RB, Monteiro SS, Picarra-Pereira MA, Teixeira AR. Engineering grapevine for increased resistance to fungal pathogens without compromising wine stability. Trends Biotechnol 2004;22:168-173

The vast majority of wine proteins have recently been identified as pathogenesis-related (PR) proteins. During the growing season, these proteins are expressed in developmentally dependent and inducible manners in grapevine leaves and grape berries, in which they are believed to play an important role in protection against fungal pathogens and possibly other stresses. Because of their inherent resistance to proteolytic attack and to the low pH values characteristic of wines, vinification can be seen as a "purification strategy" for grape PR proteins. The inevitable consequent accumulation of these proteins in wines becomes a technological nuisance because they adversely affect the clarity and stability of wines. Genetically modified vines underexpressing PR proteins would certainly lead to stable wines but would increase the plant susceptibility to fungal attack, and the actual trend seems to be in the opposite direction, that is overexpressing these proteins to obtain plants with enhanced resistance to pathogens--a trend that will probably augment problems associated with protein instability in the resulting wines.

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[22] - Vassilopoulou E, Zuidmeer L, Akkerdaas J, Tassios I, Rigby NR, Mills ENC, et al. Severe Immediate Allergic Reactions to Grapes: Part of a Lipid Transfer Protein-Associated Clinical Syndrome. Int Arch Allergy Immunol 2007;143:92-102

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.

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[23] - Diaz-Perales A, Collada C, Blanco C, Sanchez-Monge R, Carillo T, Aragoncillo C, et al. Cross-reactions in the latex-fruit syndrome: a relevant role of chitinases but not of complex asparagine-linked glycans. J Allergy Clin Immunol 1999;104:681-687

BACKGROUND: Cross-reactions between latex and plant foods (mainly fruits) have been widely reported. Although the cross-reactive components have not been well identified, class I chitinases seem to be the most credible candidates in chestnut, avocado, and banana . OBJECTIVE: We sought to evaluate the potential role of chitinases and complex glycans as cross-reactive determinants linked to latex-food allergy . METHODS: Extracts from 20 different plant foods and from latex were obtained. These preparations were immunodetected with anticomplex glycans and antichitinase sera raised in rabbits, as well as with sera from patients with latex-fruit allergy and sera from patients allergic to latex without food allergy. Immunoblot inhibition assays were carried out by using a purified class I chitinase from avocado or latex extract as inhibitors . RESULTS: Reactive proteins of approximately 30 to 45 kd (putative class I chitinases) were recognized by both specific polyclonal antibodies to chitinases and sera from patients with latex-fruit allergy in chestnut, cherimoya, passion fruit, kiwi, papaya, mango, tomato, and flour wheat extracts. Prs a 1, the major allergen and class I chitinase from avocado, and the latex extract strongly or fully inhibited IgE binding by these components when tested in immunoblot inhibition assays. Additional bands of 16 to 20 kd, 23 to 28 kd, and 50 to 70 kd were detected by the antichitinase serum but not with the patients' pooled sera. The putative 30- to 45-kd chitinases present in different food extracts did not react with a pool of sera from subjects allergic to latex but not to fruit. Very different immunodetection patterns were produced with the anticomplex glycan serum and the sera from allergic patients . CONCLUSIONS: Putative class I chitinases seem to be relevant cross-reactive components in foods associated with the latex-fruit syndrome, but do not play a specific role in allergy to latex but not to fruit. Cross-reactive carbohydrate determinants are not important structures in the context of latex-fruit cross-sensitization.

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[24] - Sarry JE, Sommerer N, Sauvage FX, Bergoin A, Rossignol M, Albagnac G, et al. Grape berry biochemistry revisited upon proteomic analysis of the mesocarp. Proteomics 2004;4:201-215

Major soluble proteins of grapevine ripe berries were extracted from six different cultivars including non vinifera, with trichloroacetic acid acetone and resolved in two-dimensional electrophoresis (2-DE) gels. About three hundred spots were detected on the 2-DE map after colloidal blue staining. From 2-DE map of cv. Gamay mesocarp, 67 proteins were identified (p > 0.95) using matrix-assisted laser desorption/ionization-mass spectrometry analysis. About 34%, 19%, and 13% of identified proteins play, respectively, a role in energy metabolism, defense, and stress response and primary metabolism. 2-DE analysis revealed considerable accumulation of dehydrin, invertase, and a putative transcription factor in the ripe fruit, in addition to pathogenesis-related proteins such as chitinase and thaumatin-like proteins previously documented as prevalent proteins in ripe berries. Actual translation of redundant transcripts of unclear function such as Grip31, Grip32, and Grip61 recently cloned in ripe grape berries was confirmed. The relative abundance of UDP-glucose pyrophosphorylase and vacuolar invertase strongly supported a key role of the apoplastic pathway of sugar loading during ripening. Comparative analysis shows that differences between cultivars were low, but different isoforms of alcohol dehydrogenase and of a transcription factor of hexose transporter were obvious in the six cultivars. Peptide mass fingerprinting suggests that the Adh isoforms would be Adh2/Adh6 or Adh2/Adh7 dimers and unambiguously shows that considerable deletion/insertion inside Adh7 are not cloning artifacts.

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[25] - Akkerdaas J, Fernandez-Rivas M, Zuidmeer L, Hefle S, Aalberse R, van Ree R. IgE binding profiles to several food LTPs of Spanish patients with apple ingestion related symptoms. Allergy Clin Immunol Int 2005;17(Suppl. 1):338-339

Background Fruit allergic individuals from the Mediterranean area are predominantly sensitized by the non-specific lipid transfer protein (nsLTP). It seems that peach LTP is the most likely sensitizing allergen, however other factors (pollen related, genetic) can not be excluded yet. Objective It was our aim to identify IgE binding profiles to different natural (n) and recombinant (r) purified LTPs and to study the pair wise correlation between amino acid sequence identity and LTP specific IgE titers. Methods Serum and clinical data (after ingestion of 6 different foods) was obtained from Spanish apple allergic patients (n=19), as was proven by SPT/ DBPCFC. Seven different LTPs (rApple, rPeach, nGrape, rStrawberry, nSunflower, nHazelnut and nMaize, also analyzed for sequence homology) were applied in RAST to determine specific-IgE titers. Results Clinical symptoms after apple ingestion ranged from no- to severe systemic reactions like anaphylaxis. LTP Sequence homologies ranged from 81% (apple/peach) to 44% (hazelnut/maize). Highest correlation observed for IgE binding:0.989 (apple:peach). Lowest correlation: 0.228 (maize/grape). RAST highest/lowest mean score: apple 6.4/maize 0.4 IU/ml respectively. Conclusion Since most patients were selected on having a true apple allergy and the amino acid sequence homology between apple and peach LTP is 81%, an IgE binding-correlation of 0.989 was to be expected. Elucidation of IgE crossreactivity patterns between the LTPs applied might predict clinical symptoms. The intriguing question remains: How do we identify the sensitizing LTP and how do we prevent the development of (severe) food allergy as result of the induction of IgE against LTP?

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[26] - Kalogeromitros DC, Makris MP, Gregoriou SG, Katoulis AC, Straurianeas NG. Sensitization to other foods in subjects with reported allergy to grapes. Allergy Asthma Proc 2006;27:68-71

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.

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[27] - Kalogeromitros DC, Makris MP, Gregoriou SG, Mousatou VG, Lyris NG, Tarassi KE, et al. Grape anaphylaxis: a study of 11 adult onset cases. Allergy Asthma Proc 2005;26:53-58

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.

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[28] - Rodriguez A, Trujillo MJ, Matheu V, Baeza ML, Zapatero L, Martinez M. Allergy to grape: a case report. Pediatr Allergy Immunol 2001;12:289-290

We report a case of a 5-year-old child who suffered an oral allergy syndrome and lip angiedema after eating grapes. We obtained a positive prick test with commercial grape extract and a positive prick-by-prick test with pulp and peel of fresh white grape (Moscatel variety) and pulp and peel of blue grape. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis followed by immunoblotting revealed specific immunoglobulin E (IgE) antibodies in the patient's serum against a 94,000 molecular-weight antigenic band. Lip open challenge was positive.

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[29] - Pastorello EA, Farioli L, Pravettoni V, Ortolani C, Fortunato D, Giuffrida G, et al. Identification of grape and wine allergens as an endochitinase 4, a lipid-transfer protein, and a thaumatin. J Allergy Clin Immunol 2003;111:350-359

BACKGROUND: Few allergic reactions to grape are reported in the literature. In some cases an association with peach and cherry allergy was observed. No IgE-mediated reactions to wine have been described, and no grape major allergens have yet been identified . OBJECTIVE: We describe several severe reactions to grape or wine. We characterized the grape major allergens and tried to identify the allergen in wine . METHODS: We collected documented histories of allergic reactions to grape and wine. Grape allergens were identified by means of SDS-PAGE and immunoblotting and purified by means of HPLC. Using amino acid sequencing and mass spectrometry, we identified the family of proteins to which the allergens belong. Cross-reactivity with peach and cherry was evaluated by means of cross-wise inhibition experiments . RESULTS: Eleven patients with reactions to grape and 3 with anaphylactic reactions to wine were recruited. The major allergens were an endochitinase 4A and a lipid-transfer protein (LTP) that was homologous to and cross-reactive with peach LTP. A 24-kd protein homologous to the cherry thaumatin-like allergen was a minor allergen. Endochitinase 4A is very likely the allergen in vino novello and in vino Fragolino . CONCLUSIONS: Grape and wine might cause severe allergic reactions in sensitive patients. The major allergens of grape are endochitinase 4A, which is also the allergen of wine, and an LTP cross-reacting with the peach major allergen.

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[30] - Karakaya G, Kalyoncu AF. Allergy to grapes. Ann Allergy Asthma Immunol 2000;84:265

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[31] - Gebhardt C, Vieths S, Gubesch M, Averbeck M, Simon JC, Treudler R. 10 kDa lipid transfer protein: the main allergenic structure in a German patient with anaphylaxis to blueberry. Allergy 2009;64:498-499

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[32] - Campina Costa S, Costa Silva I, Romeira A, Rosa S, Bartolomé Zavala B, Leria Pinto P. Grape allergy and coexisting sensitisations. Allergy 2008;63(suppl. 88):587

Background: Grape allergy is uncommon but a considerable number of allergic reactions to grape have been recently reported, particularly in the Mediterranean countries where it is widely consumed. We report two clinical cases of grape anaphylaxis. The first patient (1Pt) is a 19-year-old woman who suffered from anaphylactic reactions after grape, almond and pistachio ingestion and oral-allergy syndrome to peach and kiwi. The second patient (2Pt) is a 59-year-old woman who reported an anaphylactic reaction after grape ingestion and oral-allergy syndrome to walnuts and fig. Neither of them had symptoms with other grape products like wine or wine vinegar. Methods: Skin prick tests (SPT) were performed with extracts from almond, pistachio, walnut and hazelnut (Bial-Aristeguis). Prick-prick tests (PPT) were performed to grape, raisin, wine and wine vinegar. Specific IgE to grape, almond, pistachio, walnut and hazelnut were determined by EAST method. PPT and specific IgE to peach and kiwi were also performed for the 1Pt and PPT to fig was done for the 2Pt. Results: For the 1Pt: SPT were positive to almond, pistachio and hazelnut; PPT to grape, raisin, peach and kiwi were positive; serum specific IgE were positive against peach (2.99 kU/L), grape (0.9 kU/L), kiwi (1.1 kU/L), lipid transfer protein (LTP) from peach (3.2 kU/L) and negative (o 0.35 kU/L) against almond and pistachio. For the 2Pt: SPT were positive to walnut and hazelnut; PPT to grape, raisin, wine, wine vinegar and fig were positive; specific IgE to grape as well as to walnut and hazelnut were negative. Conclusion: We report two cases of severe IgE-mediated reactions to grape with coexisting sensitisation to other food allergens. The clinical relevance of the concomitant reactivity to other fruits points out the need to better investigate the pattern of crossreactivity in patients with grape allergy.

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[33] - Schäd SG, Trcka J, Vieths S, Scheurer S, Conti A, Trautman A. Wine Anaphylaxis in a German Patient: IgE-Mediated Allergy against a Lipid Transfer Protein of Grapes. Int Arch Allergy Immunol 2005;136:159-164

BACKGROUND: IgE-mediated allergy to grapes has very rarely been reported in patients from the Mediterranean area. Recently, endochitinase 4 and a lipid transfer protein (LTP) have been identified as major allergens in grape-allergic patients who do not have an associated pollinosis. The purpose of this case study was to identify the allergens responsible for severe anaphylactic reactions after consumption of wine, fresh grapes and raisins in a German patient . METHODS: Prick-to-prick tests and the basophil activation test (BAT) were performed to confirm allergy. Specific IgE was further analyzed by immunoblotting and inhibition tests for the determination of crossreactivity. The IgE-binding protein was subjected to N-terminal microsequencing . RESULTS: Prick-to-prick tests were positive to fresh and cooked white and blue grapes, to raisins, to white and red wine, and to grape extract. Specific IgE against grapes (f259) was 2.43 kU/l (class 2). The BAT showed specific IgE-mediated activation of basophils after stimulation with grape extract. IgE binding to a 15-kDa protein was completely inhibited by pre-incubation with recombinant cherry LTP Pru av 3. N-terminal sequencing identified this 15-kDa protein as grape LTP Vit v 1 . CONCLUSION: Our data show that sensitization to LTP can occur outside the Mediterranean area causing severe fruit allergy without association to pollinosis.

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[34] - Pravettoni V, Conti A, Farioli L, Rivolta F, Calamari A.M, Trambaioli C, et al. Identification of the major allergens of grape. 8th International Symposium on Problems of Food Allergy, Venice 2001, March 11-13

Few cases of allergic reactions to grape have been reported in the literature. Thus nothing is known on the allergenic molecules of grape nor on the cross-reactivity with other fruits. Some of the reported cases were however associated with allergy to the Prunoideae family fruits. Aim: of this study was to describe subjects with severe allergic reactions following grape ingestion and to characterize the major allergens of grape. Methods: patients (pts) with a documented clinical history of allergic reactions to grape, were evaluated by skin prick tests with fresh fruit and serum IgE antibodies to grape. IgE pattern reactivity to grape extract has been analyzed by SDS-PAGE and immunoblotting using all the sera. The identified allergens were characterized by amminoacidic sequencing. Results: 11 patients presenting anaphylactic reactions following grape ingestion were selected. The reported symptoms were: anaphylactic shock in 4 cases, of which 2 following grape ingestion and 2 following young wine assumptiom, severe asthma in 1 case, glottis oedema and angioedema in 4 cases, glottis oedema and urticaria in 2 cases, gastrointestinal symptoms and hypotension in 1 case. In 2 cases symptoms followed exercise. Most patients also were sensitised to other fruits, in particular peach and cherry. Nine out of eleven patients showed an IgE reactivity to a protein of 30 kd, eight out of eleven pts reacted to a protein of 9 kd and four pts to a protein of 24 kd. The N-terminal aminoacid sequence of the 9 kd component, analyzed in a Swiss Prot Bank, showed that this protein is a lipid transfer protein highly homologous to the peach LTP (80%). The immunoblot inhibition of the grape 9 kd protein from the peach extract demonstrated the cross-reactivity between these fruits. The N-terminal aminocid sequence of the 24 kd component showed that this protein is an osmotin homologous to the cherry thaumatin (40%). The N-terminal sequence of the 30 kD protein was blocked. Conclusions: Grape may be cause of severe allergic reactions. The major allergens of grape are a LTP highly homologous to the major allergen of peach and an osmotin protein that is homologous to the thaumatin allergen of cherry.

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[35] - Asero R, Mistrello G, Roncarolo D, Amato S. Detection of Some Safe Plant-Derived Foods for LTP-Allergic Patients. Int Arch Allergy Immunol 2007;144:57-63

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.

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[36] - Vassilopoulou E, Zuidmeer L, Akkerdaas J, Tassios I, Rigby NR, Mills ENC, et al. Severe Immediate Allergic Reactions to Grapes: Part of a Lipid Transfer Protein-Associated Clinical Syndrome. Int Arch Allergy Immunol 2007;143:92-102

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.

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[37] - Pastorello EA, Farioli L, Pravettoni V, Ortolani C, Fortunato D, Giuffrida G, et al. Identification of grape and wine allergens as an endochitinase 4, a lipid-transfer protein, and a thaumatin. J Allergy Clin Immunol 2003;111:350-359

BACKGROUND: Few allergic reactions to grape are reported in the literature. In some cases an association with peach and cherry allergy was observed. No IgE-mediated reactions to wine have been described, and no grape major allergens have yet been identified . OBJECTIVE: We describe several severe reactions to grape or wine. We characterized the grape major allergens and tried to identify the allergen in wine . METHODS: We collected documented histories of allergic reactions to grape and wine. Grape allergens were identified by means of SDS-PAGE and immunoblotting and purified by means of HPLC. Using amino acid sequencing and mass spectrometry, we identified the family of proteins to which the allergens belong. Cross-reactivity with peach and cherry was evaluated by means of cross-wise inhibition experiments . RESULTS: Eleven patients with reactions to grape and 3 with anaphylactic reactions to wine were recruited. The major allergens were an endochitinase 4A and a lipid-transfer protein (LTP) that was homologous to and cross-reactive with peach LTP. A 24-kd protein homologous to the cherry thaumatin-like allergen was a minor allergen. Endochitinase 4A is very likely the allergen in vino novello and in vino Fragolino . CONCLUSIONS: Grape and wine might cause severe allergic reactions in sensitive patients. The major allergens of grape are endochitinase 4A, which is also the allergen of wine, and an LTP cross-reacting with the peach major allergen.

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[38] - Asero R, Mistrello G, Roncarolo D, Amato S. Detection of Some Safe Plant-Derived Foods for LTP-Allergic Patients. Int Arch Allergy Immunol 2007;144:57-63

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.

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[39] - Sankian M, Varasteh A, Pazouki N, Mahmoudi M. Sequence homology: A poor predictive value for profilins cross-reactivity. Clin Mol Allergy 2005;3:13

BACKGROUND: Profilins are highly cross-reactive allergens which bind IgE antibodies of almost 20% of plant-allergic patients. This study is aimed at investigating cross-reactivity of melon profilin with other plant profilins and the role of the linear and conformational epitopes in human IgE cross-reactivity . METHODS: Seventeen patients with melon allergy were selected based on clinical history and a positive skin prick test to melon extract. Melon profilin has been cloned and expressed in E. coli. The IgE binding and cross-reactivity of the recombinant profilin were measured by ELISA and inhibition ELISA. The amino acid sequence of melon profilin was compared with other profilin sequences. A combination of chemical cleavage and immunoblotting techniques were used to define the role of conformational and linear epitopes in IgE binding. Comparative modeling was used to construct three-dimensional models of profilins and to assess theoretical impact of amino acid differences on conformational structure . RESULTS: Profilin was identified as a major IgE-binding component of melon. Alignment of amino acid sequences of melon profilin with other profilins showed the most identity with watermelon profilin. This melon profilin showed substantial cross-reactivity with the tomato, peach, grape and Cynodon dactylon (Bermuda grass) pollen profilins. Cantaloupe, watermelon, banana and Poa pratensis (Kentucky blue grass) displayed no notable inhibition. Our experiments also indicated human IgE only react with complete melon profilin. Immunoblotting analysis with rabbit polyclonal antibody shows the reaction of the antibody to the fragmented and complete melon profilin. Although, the well-known linear epitope of profilins were identical in melon and watermelon, comparison of three-dimensional models of watermelon and melon profilins indicated amino acid differences influence the electric potential and accessibility of the solvent-accessible surface of profilins that may markedly affect conformational epitopes . CONCLUSION: Human IgE reactivity to melon profilin strongly depends on the highly conserved conformational structure, rather than a high degree of amino acid sequence identity or even linear epitopes identity.

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[40] - Ahrazem O, Ibáñez D, López-Torrejón G, Sánchez-Monge R, Sastre J, Lombardero M, et al. Lipid Transfer Proteins and Allergy to Oranges. Int Arch Allergy Immunol 2005;137:201-210

BACKGROUND: Lipid transfer proteins (LTPs) are relevant fruit allergens, recently proposed as model plant food allergens. No citrus fruit allergen has been characterized to date. We sought to identify and isolate citrus fruit LTPs and to explore their relevance in orange allergy . METHODS: Twenty-seven patients, showing mainly oral allergy syndrome after orange ingestion, as well as positive prick responses and serum-specific IgE levels to orange, were selected. Natural orange and lemon LTPs, as well as a recombinant orange LTP isoform expressed in Pichia pastoris, were isolated by chromatographic methods and characterized by N-terminal amino acid sequencing and matrix-assisted laser desorption/ionizaion mass spectrometry, and DNA sequencing of the corresponding cDNA in the case of the recombinant allergen. Specific IgE determination, immunodetection, ELISA-inhibition assays and in vivo skin prick tests (SPTs) were performed with all three purified allergens and with the major peach LTP allergen, Pru p 3 . RESULTS: The natural allergens purified from orange (nCit s 3) and lemon (nCit l 3) showed very similar N-terminal amino acid sequences (18 out of 20 identical residues), typical of LTPs, and molecular masses of 9,610 and 9,618 Da, respectively. The recombinant orange isoform (rCit s 3) expressed in P. pastoris (16 out of 20 residues identical to its natural counterpart in the N-terminal region) presented 92 amino acid residues and 9,463 Da, and 67% sequence identity with rPru p 3. Of the 27 sera analyzed, specific IgE to the purified allergens was found in 54% for nCit l 3, 48% for nCit s 3, 46% for rCit s 3 and 37% for rPru p 3. Positive SPT responses were obtained in 7 out of 26 patients tested for nCit s 3, 3 out of 8 for nCit l 3 and 10 out of 26 for nPru p 3. ELISA-inhibition assays showed an equivalent IgE-binding pattern for the natural and recombinant orange LTPs, and IgE cross-reactivity among the purified orange, lemon and peach LTP allergens . CONCLUSIONS: Members of the LTP allergen family are involved in allergy to oranges, displaying positive in vitro and in vivo reactions in 30-50% of the patients studied. Both orange and lemon allergens show cross-reactivity with the major peach allergen Pru p 3.

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[41] - Pocock KF, Hayasaka Y, McCarthy MG, Waters EJ. Thaumatin-like proteins and chitinases, the haze-forming proteins of wine, accumulate during ripening of grape (Vitis vinifera) berries and drought stress does not affect the final levels per berry at maturity. J Agric Food Chem 2000;48:1637-1643

Thaumatin-like proteins and chitinases, which are pathogenesis-related (PR) proteins, were the major soluble protein components of grapes from five cultivars of Vitis vinifera. This dominance of PR proteins was apparent at berry softening (veraison) and then throughout berry development for the Muscat of Alexandria, Sultana, and Shiraz cultivars and in the berries of the Sauvignon Blanc and Pinot Noir cultivars examined at commercial maturity. The M(r) of the major thaumatin-like protein from Muscat of Alexandria grapes was 21 272, and those of the three major chitinases from this cultivar, ChitB, ChitC, and ChitD, were 25 588, 25 410, and 25 457, respectively. The vines in the study were irrigated and showed no obvious signs of disease. Shiraz vines that had not been irrigated throughout the season were clearly water stressed, but had levels of PR proteins in the berry similar to vines that had been fully irrigated. It appears that the production of PR proteins that cause protein instability in wines by grapes may be little influenced by environmental conditions.

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[42] - Ferreira RB, Monteiro SS, Picarra-Pereira MA, Teixeira AR. Engineering grapevine for increased resistance to fungal pathogens without compromising wine stability. Trends Biotechnol 2004;22:168-173

The vast majority of wine proteins have recently been identified as pathogenesis-related (PR) proteins. During the growing season, these proteins are expressed in developmentally dependent and inducible manners in grapevine leaves and grape berries, in which they are believed to play an important role in protection against fungal pathogens and possibly other stresses. Because of their inherent resistance to proteolytic attack and to the low pH values characteristic of wines, vinification can be seen as a "purification strategy" for grape PR proteins. The inevitable consequent accumulation of these proteins in wines becomes a technological nuisance because they adversely affect the clarity and stability of wines. Genetically modified vines underexpressing PR proteins would certainly lead to stable wines but would increase the plant susceptibility to fungal attack, and the actual trend seems to be in the opposite direction, that is overexpressing these proteins to obtain plants with enhanced resistance to pathogens--a trend that will probably augment problems associated with protein instability in the resulting wines.

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[43] - Romero I, Sanchez-Ballesta MT, Maldonado R, Escribano MI, Merodio C. Expression of class I chitinase and ß-1,3-glucanase genes and postharvest fungal decay control of table grapes by high CO2 pretreatment. Postharvest Biol Technol 2006;41:9-15

The effect of pretreatment with 20% CO2 plus 20% O2 for 3 days was studied with regard to its effectiveness on natural postharvest decay control and its possible induction of specific PR genes in table grapes. Full-length cDNAs encoding a class I chitinase (Vcchit1b) and ß-1,3-glucanase (Vcgns1) were isolated from table grapes (Vitis vinifera L. cv. ŒCardinal‚). Our results indicate that this short-term high CO2 treatment had a residual effect and significantly reduced decay incidence of table grapes during low temperature storage and upon transfer to 20 °C. Our results indicate that during low temperature storage the expression pattern differed between the two tested PR genes. So, while the abundance of Vcgns1 transcript increased sharply at the beginning of storage at 0 °C, the increase in Vcchit1b mRNA levels was paralleled by the change in total decay. High CO2 pretreatment restrained the up-regulation of Vcgns1 gene expression and delayed the accumulation of Vcchit1b transcript as compared with non-treated grapes. Upon transfer to 20 °C after 33 days of cold storage, when attainment of maximum total decay was observed, there was a sharp increase in the accumulation of Vcchit1b mRNA in both treated and non-treated grapes, which was higher in the non-treated ones. Our results point out that the expression of class I chitinase and ß-1,3-glucanase genes is not enhanced in CO2-treated grapes which control total fungal decay. These results suggest, then, that the efficacy of high CO2 pretreatment in reducing total fungal decay is not mediated by induction of the above-mentioned PR genes.

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[44] - Vassilopoulou E, Zuidmeer L, Akkerdaas J, Tassios I, Rigby NR, Mills ENC, et al. Severe Immediate Allergic Reactions to Grapes: Part of a Lipid Transfer Protein-Associated Clinical Syndrome. Int Arch Allergy Immunol 2007;143:92-102

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.

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[45] - Vassilopoulou E, Rigby N, Moreno FJ, Zuidmeer L, Akkerdaas J, Tassios I, et al. Effect of in vitro gastric and duodenal digestion on the allergenicity of grape lipid transfer protein. J Allergy Clin Immunol 2006;118:473-480

BACKGROUND: Severe grape allergy has been linked to lipid transfer protein (LTP) sensitization. LTPs are known to be resistant to pepsin digestion, although the effect of gastroduodenal digestion on its allergenicity has not been reported . OBJECTIVE: We sought to investigate the effect of gastric and gastroduodenal digestion on the allergenic activity of grape LTP . METHODS: The proteolytic stability of grape LTP was investigated by using an in vitro model of gastrointestinal digestion. The allergenicity of LTP and its digesta was assessed in vitro by means of IgE immunoblotting, RASTs, and in vivo skin prick tests in the same patients with grape allergy . RESULTS: Grape LTP was resistant to gastric digestion, and yielded a 6000-d relative molecular mass C-terminally trimmed fragment after duodenal digestion. This fragment retained the in vitro IgE reactivity of the intact protein. Inclusion of phosphatidylcholine during gastric digestion protected the LTP to a limited extent against digestion. Digestion did not affect the in vivo (skin prick test) biologic activity of LTP . CONCLUSION: The allergenic activity of grape LTP was highly resistant to in vitro digestion. This property might facilitate sensitization through the gastrointestinal tract and might also potentiate the ability of LTPs to elicit severe allergic reactions in sensitized individuals. CLINICAL IMPLICATIONS: Purified natural allergens will facilitate the development of component-resolved diagnostic approaches, including allergen chips. This study contributes to our understanding of the role digestion plays in symptom elicitation in true food allergy.

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[46] - Smole U, Bublin M, Radauer C, Ebner C, Scheiner O, Breiteneder H. Allergenic Fruit TLPs Possess Different Degrees of IgE Crossreactivity. AAAAI 62nd Annual Meeting, Miami, 3-7 March 2006, Poster n°195

RATIONALE: Thaumatin-like proteins (TLPs) are important allergens of a number of plant foods. We aimed to examine the IgE cross-reactivity between the apple TLP Mal d 2 and TLPs from kiwi (Act c2), grape (VvTLP), and cherry (Pru av 2) METHODS: Amino acid sequences of apple, cherry, kiwi, and grape TLPs were aligned. The TLPs were purified. IgE ELISA and ELISA inhibitions were carried out using sera from 46 apple allergic patients. The relevance of N-glycosylation for IgE-binding was investigated by inhibition with the oligosaccharide BSA-MUXF RESULTS: Sequence alignments showed 33% identity of Mal d 2 to Act c 2, 35% to VvTLP, and 69 % to Pru av 2. Mal d 2 was IgE reactive with a prevalence of 39% (18/46). Nine of these 18 patients recognized N-glycan epitopes on Mal d 2, the 9 remaining showed binding to protein epitopes Two of the 9 protein-specific sera had IgE to all four TLPs, 6/9 to Mal d 2, Act c 2, and Pru av 2, and one to Mal d 2 and Pru av 2. In addition, Mal d 2 and Pru av 2 showed a high extent of cross-reactivity CONCLUSIONS: The glycoallergen Mal d 2 shares cross-reactive epitopes with other TLPs that encompass the Mal d 2 polypeptide and its N-glycan structure. Inhibition of IgE-Mal d 2 interactions with Pru av 2 demonstrated that many of the epitopes of Mal d 2 were cross-reactive with epitopes on Pru av 2 This work was supported by the Austrian Science Fund grant SFBF01802 Funding: Austrian Science Fund grant SFB-F01802

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[47] - Lahoz C, Cortegano I, Minguez A, Del Pozo V, Civantos E, Cardaba B, et al. Cup a 3, Major Allergen From Cupressus Arizonica: Cloning and Expression in Pichia Pastoris. AAAAI 58th Annual Meeting, New York, 1-6 March, 2002, Poster n°397

The Cupressaceae family is a relevant source of pollen allergens in the Mediterranean area responsible for frequent winter respiratory allergies. We have previously cloned the major allergen from Cupressus arizonica (Cup a 1): Clin. Exp. Allergy 2000;30:1750-1758, and now we describe the cloning and expression of an important allergen from this family: Cup a 3 which is reactive with more than 90% of cupressaceae patients, being considered as a major antigen with similar reactivity to Cup a1. The theoretical molecular weight for the cloned protein is 21 kDa, the calculated pI is 4.82 and several phosphorylation sites are found in the amino acid sequence. The nucleotides sequence NCBI Nucleotide Database (AJ294411, Cup a 3) has 96% homology with mountain cedar allergen Jun a 3, 93% with Vitis vinifera a thaumatin-like protein and 89% with Atriplex nummularia an osmotin-like protein. This allergen may be included in Group 5 of pathogenesis-related proteins. Recombinant Cup a 3 has been cloned in pBluescript and expressed in E. coli as a fusion protein with GST but the yield was poor. To improve it, Cup a 3 has been expressed in Pichia pastoris system using pPCIZA plasmid. A cDNA encoding Cup a 3, fused to a - factor peptide using the pPCIZA vector has been inserted into the yeast genome under the control of the AOX1 promoter. After induction with methanol, the protein is secreted into the extracellular medium. The IgE binding properties of the recombinant protein produced in yeast have been tested in immunoblot assays using sera from allergic patients. The excellent production of recombinant Cup a 3 in yeast may contribute to the standardization of the allergens used for diagnosis and immunotherapy. The nucleotide sequence is: 1 gtgaagtttg atataaagaa ccagtgcggg tacactgtct gggcagcggg gttgcccgga 61 ggagggaagg agtttgacca ggggcagaca tggacggtta atttggcggc gggcacagcg 121 tcggcaaggt tctggggacg aacgggctgc actttcgatg cgagcgggaa aggaagctgc 181 cggagcggtg actgcggcgg gcaactgagc tgcacagtct ccggagcagt tcccgcaacg 241 ctggcagagt acacgcagag cgaccaggac tactacgacg tctccctcgt cgatggcttc 301 aacattcctc ttgccatcaa cccaaccaat acaaaatgca ctgcccctgc ctgcaaggct 361 gacattaatg cagtgtgccc ttccgagttg aaggttgatg gcggatgcaa cagtgcctgc 421 aatgtcttac aaactgatca gtattgctgc agaaatgcgt atgttaataa ctgccctgcc 481 acgaattact ccaagatatt caagaaccag tgccctcagg cttatagcta tgctaaggat 541 gacactgcca ctttcgcttg cgcctctggt accgactaca gtattgtatt ctgcccc.

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[48] - Pastorello EA, Farioli L, Pravettoni V, Ortolani C, Fortunato D, Giuffrida G, et al. Identification of grape and wine allergens as an endochitinase 4, a lipid-transfer protein, and a thaumatin. J Allergy Clin Immunol 2003;111:350-359

BACKGROUND: Few allergic reactions to grape are reported in the literature. In some cases an association with peach and cherry allergy was observed. No IgE-mediated reactions to wine have been described, and no grape major allergens have yet been identified . OBJECTIVE: We describe several severe reactions to grape or wine. We characterized the grape major allergens and tried to identify the allergen in wine . METHODS: We collected documented histories of allergic reactions to grape and wine. Grape allergens were identified by means of SDS-PAGE and immunoblotting and purified by means of HPLC. Using amino acid sequencing and mass spectrometry, we identified the family of proteins to which the allergens belong. Cross-reactivity with peach and cherry was evaluated by means of cross-wise inhibition experiments . RESULTS: Eleven patients with reactions to grape and 3 with anaphylactic reactions to wine were recruited. The major allergens were an endochitinase 4A and a lipid-transfer protein (LTP) that was homologous to and cross-reactive with peach LTP. A 24-kd protein homologous to the cherry thaumatin-like allergen was a minor allergen. Endochitinase 4A is very likely the allergen in vino novello and in vino Fragolino . CONCLUSIONS: Grape and wine might cause severe allergic reactions in sensitive patients. The major allergens of grape are endochitinase 4A, which is also the allergen of wine, and an LTP cross-reacting with the peach major allergen.

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[49] - Vassilopoulou E, Zuidmeer L, Akkerdaas J, Tassios I, Rigby NR, Mills ENC, et al. Severe Immediate Allergic Reactions to Grapes: Part of a Lipid Transfer Protein-Associated Clinical Syndrome. Int Arch Allergy Immunol 2007;143:92-102

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.

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[50] - Kalogeromitros DC, Makris MP, Gregoriou SG, Mousatou VG, Lyris NG, Tarassi KE, et al. Grape anaphylaxis: a study of 11 adult onset cases. Allergy Asthma Proc 2005;26:53-58

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.

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[51] - Pétrus M, Malandain H. Allergie alimentaire au raisin. Une nouvelle observation chez un enfant de 4 ans. Rev Fr Allergol Immunol Clin 2002;42:806-809

L'allergie au raison est rare : trois observations pédiatriques sont connues et une vingtaine d'observations chez l'adulte. Les motifs de consultation sont, le plus souvent, un syndrome oral ; mais, des manifestations plus graves sont possibles : asthme, anaphylaxie à l'effort, choc anaphylactique. Les auteurs rapportent l'observation d'un garçon de 4 ans, présentant une allergie au raisin, dont les symptômes cliniques sont limités à un syndrome oral. Le diagnostic est affirmé par les tests cutanés au raisin natif, le test labial et le dosage des IgE sériques spécifiques. Cette allergie s'intègre dans le cadre d'un syndrome d'allergies multiples : acariens, pollens de graminées, blanc d'uf, poisson, noix de coco, kiwi, amande, latex. Les relations moléculaires, pouvant expliquer cette association d'allergies, sont discutées.

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[52] - Pastorello EA, Farioli L, Pravettoni V, Ortolani C, Fortunato D, Giuffrida G, et al. Identification of grape and wine allergens as an endochitinase 4, a lipid-transfer protein, and a thaumatin. J Allergy Clin Immunol 2003;111:350-359

BACKGROUND: Few allergic reactions to grape are reported in the literature. In some cases an association with peach and cherry allergy was observed. No IgE-mediated reactions to wine have been described, and no grape major allergens have yet been identified . OBJECTIVE: We describe several severe reactions to grape or wine. We characterized the grape major allergens and tried to identify the allergen in wine . METHODS: We collected documented histories of allergic reactions to grape and wine. Grape allergens were identified by means of SDS-PAGE and immunoblotting and purified by means of HPLC. Using amino acid sequencing and mass spectrometry, we identified the family of proteins to which the allergens belong. Cross-reactivity with peach and cherry was evaluated by means of cross-wise inhibition experiments . RESULTS: Eleven patients with reactions to grape and 3 with anaphylactic reactions to wine were recruited. The major allergens were an endochitinase 4A and a lipid-transfer protein (LTP) that was homologous to and cross-reactive with peach LTP. A 24-kd protein homologous to the cherry thaumatin-like allergen was a minor allergen. Endochitinase 4A is very likely the allergen in vino novello and in vino Fragolino . CONCLUSIONS: Grape and wine might cause severe allergic reactions in sensitive patients. The major allergens of grape are endochitinase 4A, which is also the allergen of wine, and an LTP cross-reacting with the peach major allergen.

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[53] - Gaspar A, Raulf-Heimsoth M, Pires G, Rihs HP, Yeang HY, Matos V, et al. Latex allergen sensitization patterns in different risk groups and latex-fruit syndrome patients from Portugal. EAACI 23th Congress, Amsterdam, 12-16 June, 2004, Poster n°1188

Background: Latex allergy has been recognized as a clinically important health problem, mainly in some risk groups: spina bifida (SB), other congenital malformations submitted to multiple surgeries (MS) and health care workers (HCW). Purpose: To study IgE-binding reactivity to latex allergens, by using recombinant and natural allergens, in latex-allergic patients from different risk groups including patients with latex-fruit syndrome (LFS). Material and Methods: We selected sera of 51 latex-allergic patients within different risk groups: 20 with SB, 10 MS and 21 HCW; all these patients had positive skin prick tests with commercial latex extract (ALK-Abelló) and serum latex-specific IgE determined by UniCAP®(Pharmacia Diagnostics). Sixteen out of the 51 patients had LFS. A panel of single recombinant latex allergens was coupled to ImmunoCAPs (CAP system®) and the isolated natural allergen nHev b 2 was coupled on paper disks (EAST testing). This panel comprised rHev b 1, nHev b 2, rHev b 3, rHev b 5, rHev b 6.01, rHev b 7, rHev b 8, rHev b 9, rHev b 10 and rHev b 11. The recombinant allergens were produced as fusion protein with maltose-binding protein (MBP) in E. coli. MBP coupled on ImmunoCAPs served as control. Specific IgE values of >0.35kU/l were considered positive. Major allergen is defined if produces a positive IgE response in more than 50% of the tested group. Results: Recombinant Hev b 1 specific IgE antibodies were detected in 70% sera from SB, 30% from MS, 5% from HCW, and in 13% sera from LFS patients. For nHev b 2: SB-69%, MS-71%, HCW-71% and LFS-75%. For rHev b 3: SB-50%, MS-20%, HCW-10% and LFS-13%. For rHev b 5: SB-55%, MS-40%, HCW-62% and LFS-75%. For rHev b 6.01: SB-45%, MS-30%, HCW-76% and LFS-81%. For rHev b 7: SB-33%, MS-0%, HCW-16% and LFS-27%. For rHev b 8: SB-10%, MS-0%, HCW-5% and LFS-6%. For rHev b 9 and rHev b 10: SB-0%, MS-0%, HCW-5% and LFS-7%. For rHev b 11: SB-7%, MS-0%, HCW-5% and LFS-7%. Conclusions: The different routes of exposure influence the IgE antibody pattern. The major latex allergens identified in SB were Hev b 1, Hev b 2, Hev b 3 and Hev b 5, being Hev b 1 the most important one. The major allergen identified in MS was Hev b 2. For occupational exposure route, the major latex allergens identified in HCW were Hev b 2, Hev b 5 and Hev b 6.01, being prohevein the most important one. Regarding cross-reactivity with foods, the major allergens identified in LFS were Hev b 2, Hev b 5 and Hev b 6.01.

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[54] - MacLean J. Allergy to grapes. Ann Allergy Asthma Immunol 2000;84:265-266

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[55] - Gaspar A, Pires G, Marques S, Romeira AM, Godinho N, Matos V, et al. Prevalence and risk factors for latex-fruit syndrome in patients with latex allergy. EAACI 22th Congress, Paris, 7-11 June, 2003, Poster n°31

Background: The association of latex allergy and allergy to plant-derived foods is called latex-fruit syndrome (LFS). There are no studies concerning risk factors for LFS in latex-allergic populations including different risk groups. Purpose: To investigate the prevalence and risk factors for LFS in patients with latex allergy. Material and Methods: We studied 53 latex-allergic patients, mean age of 25.7 (±15.8) years and male/female ratio of 0.4/1, belonging to different risk groups: 14 with spina bifida (SB), 11 submitted to multiple surgeries without SB (MS) and 28 health care workers (HCW). All patients performed: questionnaire; skin prick tests (SPT) with common aeroallergens, five commercial latex extracts and foods with known cross reactivity with latex (commercial extracts and fresh foods); serum total IgE (AlaSTAT®, DPC-Amerlab) and latex specific IgE (UniCAP®, Pharmacia Diagnostics). LFS was defined if both positive clinical history and positive food SPT. RESULTS: The prevalence of LFS in latex-allergic patients was 30%. The foods implicated were: chestnut-69% (11), banana-38% (6), avocado, kiwi and peach-25% (4), passion fruit and pineapple-19% (3), papaya, apricot and melon-13% (2), mango, fig, grape, tomato, spinach and manioc-6% (1). The LFS clinical symptoms were: anaphylaxis-56% (9), urticaria-25% (4) and oral allergy syndrome-19% (3). Almost all the patients with LFS were HCW. The prevalence of LFS in HCW achieved 50% (14). The non HCW were a SB teenager, and an adult with MS. Comparing HCW with LFS (14) and HCW without LFS (14), we found a relation between LFS and higher levels of latex specific IgE (median: 15.0 vs. 0.5kU/l; p<0.01). HCW with CAP-class “ 3 had LFS in 75%, against 31% in HCW with CAP class <3 (p=0.02). Age, sex, personal and familial allergic history, number of surgical interventions, years of occupational exposure, atopy and total IgE were not associated with LFS. CONCLUSIONS: LFS concerns essentially the latex-allergic HCW, being very frequent in this group. This finding is consistent with literature reports, and is supported by the different profiles of allergen sensitisation related with exposure route (major latex allergens of HCW are the ones implicated in cross-reactivity). Latex sensitisation with CAP-class “ 3 is a risk factor for LFS in HCW group. LFS was revealed in most cases by anaphylaxis, emphasizing the importance of diagnosing this potentially life- threatening syndrome.

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[56] - Kalogeromitros DC, Makris MP, Gregoriou SG, Katoulis AC, Straurianeas NG. Sensitization to other foods in subjects with reported allergy to grapes. Allergy Asthma Proc 2006;27:68-71

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.

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[57] - Kalogeromitros DC, Makris MP, Gregoriou SG, Mousatou VG, Lyris NG, Tarassi KE, et al. Grape anaphylaxis: a study of 11 adult onset cases. Allergy Asthma Proc 2005;26:53-58

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.

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[58] - Rodriguez A, Matheu V, Trujillo MJ, Martinez MI, Baeza ML, Barranco R, et al. Grape allergy in paediatric population. Allergy 2004;59:364

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[59] - Schäd SG, Trcka J, Vieths S, Scheurer S, Conti A, Trautman A. Wine Anaphylaxis in a German Patient: IgE-Mediated Allergy against a Lipid Transfer Protein of Grapes. Int Arch Allergy Immunol 2005;136:159-164

BACKGROUND: IgE-mediated allergy to grapes has very rarely been reported in patients from the Mediterranean area. Recently, endochitinase 4 and a lipid transfer protein (LTP) have been identified as major allergens in grape-allergic patients who do not have an associated pollinosis. The purpose of this case study was to identify the allergens responsible for severe anaphylactic reactions after consumption of wine, fresh grapes and raisins in a German patient . METHODS: Prick-to-prick tests and the basophil activation test (BAT) were performed to confirm allergy. Specific IgE was further analyzed by immunoblotting and inhibition tests for the determination of crossreactivity. The IgE-binding protein was subjected to N-terminal microsequencing . RESULTS: Prick-to-prick tests were positive to fresh and cooked white and blue grapes, to raisins, to white and red wine, and to grape extract. Specific IgE against grapes (f259) was 2.43 kU/l (class 2). The BAT showed specific IgE-mediated activation of basophils after stimulation with grape extract. IgE binding to a 15-kDa protein was completely inhibited by pre-incubation with recombinant cherry LTP Pru av 3. N-terminal sequencing identified this 15-kDa protein as grape LTP Vit v 1 . CONCLUSION: Our data show that sensitization to LTP can occur outside the Mediterranean area causing severe fruit allergy without association to pollinosis.

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[60] - Kalogeromitros DC, Makris MP, Gregoriou SG, Mousatou VG, Lyris NG, Tarassi KE, et al. Grape anaphylaxis: a study of 11 adult onset cases. Allergy Asthma Proc 2005;26:53-58

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.

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[61] - Kalogeromitros DC, Makris MP, Gregoriou SG, Katoulis AC, Straurianeas NG. Sensitization to other foods in subjects with reported allergy to grapes. Allergy Asthma Proc 2006;27:68-71

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.

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[62] - Kalogeromitros DC, Makris MP, Gregoriou SG, Mousatou VG, Lyris NG, Tarassi KE, et al. Grape anaphylaxis: a study of 11 adult onset cases. Allergy Asthma Proc 2005;26:53-58

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.

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[63] - Guinnepain MT, Rassemont R, Laurent J. Le raisin est aussi un trophallergène. Rev Fr Allergol Immunol Clin 1997;37:400

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[64] - Kalogeromitros DC, Makris MP, Gregoriou SG, Mousatou VG, Lyris NG, Tarassi KE, et al. Grape anaphylaxis: a study of 11 adult onset cases. Allergy Asthma Proc 2005;26:53-58

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.

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[65] - Mur P, Feo Brito F, Bartolome B, Galindo PA, Gomez E, Borja J, et al. Simultaneous allergy to vine pollen and grape. J Investig Allergol Clin Immunol 2006;16:271-273

We report the case of an 18-year-old female student suffering from seasonal rhinoconjunctivitis with sensitization to pollens from vine and also from grass, olive, and Chenopodiaceae plants who had recently developed episodes of itching, maculopapular rash, and facial angioedema after eating grapes. Testing revealed positive reactions to vine pollen and grapes, and specific IgE were found for both allergens. Immunoblotting and inhibition assays revealed cross-reactivity between the allergenic structures of vine pollen and grape fruit and also among botanically unrelated pollens.

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[66] - Kalogeromitros DC, Makris MP, Gregoriou SG, Katoulis AC, Straurianeas NG. Sensitization to other foods in subjects with reported allergy to grapes. Allergy Asthma Proc 2006;27:68-71

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.

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[67] - Schäd SG, Trcka J, Vieths S, Scheurer S, Conti A, Trautman A. Wine Anaphylaxis in a German Patient: IgE-Mediated Allergy against a Lipid Transfer Protein of Grapes. Int Arch Allergy Immunol 2005;136:159-164

BACKGROUND: IgE-mediated allergy to grapes has very rarely been reported in patients from the Mediterranean area. Recently, endochitinase 4 and a lipid transfer protein (LTP) have been identified as major allergens in grape-allergic patients who do not have an associated pollinosis. The purpose of this case study was to identify the allergens responsible for severe anaphylactic reactions after consumption of wine, fresh grapes and raisins in a German patient . METHODS: Prick-to-prick tests and the basophil activation test (BAT) were performed to confirm allergy. Specific IgE was further analyzed by immunoblotting and inhibition tests for the determination of crossreactivity. The IgE-binding protein was subjected to N-terminal microsequencing . RESULTS: Prick-to-prick tests were positive to fresh and cooked white and blue grapes, to raisins, to white and red wine, and to grape extract. Specific IgE against grapes (f259) was 2.43 kU/l (class 2). The BAT showed specific IgE-mediated activation of basophils after stimulation with grape extract. IgE binding to a 15-kDa protein was completely inhibited by pre-incubation with recombinant cherry LTP Pru av 3. N-terminal sequencing identified this 15-kDa protein as grape LTP Vit v 1 . CONCLUSION: Our data show that sensitization to LTP can occur outside the Mediterranean area causing severe fruit allergy without association to pollinosis.

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[68] - Kalogeromitros DC, Makris MP, Gregoriou SG, Mousatou VG, Lyris NG, Tarassi KE, et al. Grape anaphylaxis: a study of 11 adult onset cases. Allergy Asthma Proc 2005;26:53-58

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.

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[69] - Senna G, Mistrello G, Roncarolo D, Crivellaro M, Bonadonna P, Schiappoli M, et al. Exercise-induced anaphylaxis to grape. Allergy 2001;56:1235-1236

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[70] - Borghesan F, Basso D, Chieco Bianchi F, Favero E, Plebani M. Allergy to wine. Allergy 2004;59:1135-1136

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[71] - Campina Costa S, Costa Silva I, Romeira A, Rosa S, Bartolomé Zavala B, Leria Pinto P. Grape allergy and coexisting sensitisations. Allergy 2008;63(suppl. 88):587

Background: Grape allergy is uncommon but a considerable number of allergic reactions to grape have been recently reported, particularly in the Mediterranean countries where it is widely consumed. We report two clinical cases of grape anaphylaxis. The first patient (1Pt) is a 19-year-old woman who suffered from anaphylactic reactions after grape, almond and pistachio ingestion and oral-allergy syndrome to peach and kiwi. The second patient (2Pt) is a 59-year-old woman who reported an anaphylactic reaction after grape ingestion and oral-allergy syndrome to walnuts and fig. Neither of them had symptoms with other grape products like wine or wine vinegar. Methods: Skin prick tests (SPT) were performed with extracts from almond, pistachio, walnut and hazelnut (Bial-Aristeguis). Prick-prick tests (PPT) were performed to grape, raisin, wine and wine vinegar. Specific IgE to grape, almond, pistachio, walnut and hazelnut were determined by EAST method. PPT and specific IgE to peach and kiwi were also performed for the 1Pt and PPT to fig was done for the 2Pt. Results: For the 1Pt: SPT were positive to almond, pistachio and hazelnut; PPT to grape, raisin, peach and kiwi were positive; serum specific IgE were positive against peach (2.99 kU/L), grape (0.9 kU/L), kiwi (1.1 kU/L), lipid transfer protein (LTP) from peach (3.2 kU/L) and negative (o 0.35 kU/L) against almond and pistachio. For the 2Pt: SPT were positive to walnut and hazelnut; PPT to grape, raisin, wine, wine vinegar and fig were positive; specific IgE to grape as well as to walnut and hazelnut were negative. Conclusion: We report two cases of severe IgE-mediated reactions to grape with coexisting sensitisation to other food allergens. The clinical relevance of the concomitant reactivity to other fruits points out the need to better investigate the pattern of crossreactivity in patients with grape allergy.

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[72] - Sbornik M, Rakoski J, Mempel M, Ollert M, Ring J. IgE-mediated type-I-allergy against red wine and grapes. Allergy 2007;62:1339-1340

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[73] - Pastorello EA, Farioli L, Pravettoni V, Ortolani C, Fortunato D, Giuffrida G, et al. Identification of grape and wine allergens as an endochitinase 4, a lipid-transfer protein, and a thaumatin. J Allergy Clin Immunol 2003;111:350-359

BACKGROUND: Few allergic reactions to grape are reported in the literature. In some cases an association with peach and cherry allergy was observed. No IgE-mediated reactions to wine have been described, and no grape major allergens have yet been identified . OBJECTIVE: We describe several severe reactions to grape or wine. We characterized the grape major allergens and tried to identify the allergen in wine . METHODS: We collected documented histories of allergic reactions to grape and wine. Grape allergens were identified by means of SDS-PAGE and immunoblotting and purified by means of HPLC. Using amino acid sequencing and mass spectrometry, we identified the family of proteins to which the allergens belong. Cross-reactivity with peach and cherry was evaluated by means of cross-wise inhibition experiments . RESULTS: Eleven patients with reactions to grape and 3 with anaphylactic reactions to wine were recruited. The major allergens were an endochitinase 4A and a lipid-transfer protein (LTP) that was homologous to and cross-reactive with peach LTP. A 24-kd protein homologous to the cherry thaumatin-like allergen was a minor allergen. Endochitinase 4A is very likely the allergen in vino novello and in vino Fragolino . CONCLUSIONS: Grape and wine might cause severe allergic reactions in sensitive patients. The major allergens of grape are endochitinase 4A, which is also the allergen of wine, and an LTP cross-reacting with the peach major allergen.

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[74] - Armentia A. Adverse reactions to wine: think outside the bottle. Curr Opin Allergy Clin Immunol 2008;8:266-269

PURPOSE OF REVIEW: Wine contains chemical and biological contaminants. Symptoms such as facial flushing, asthma and oral allergic swelling and burning (oral syndrome) have been attributed to these contaminants and food additives. Their clinical implications should be known. RECENT FINDINGS: Recent studies have reported a high prevalence of hypersensitivity symptoms after intake of alcoholic drinks in the general population. Red wine was the most common beverage implicated. Wine contains many contaminants. Some of them come from Hymenoptera insects that fall into the wine when grapes are collected and pressed. We have found patients with allergic symptoms related to wine consumption who are sensitized to Hymenoptera venom without previous stings. The aim of this study is to assess the potential importance of their sensitization to Hymenoptera antigens as the cause of their symptoms and also to comment on other recent studies on wine hypersensitivity. SUMMARY: We found patients with allergic symptoms related to wine consumption who are sensitized to Hymenoptera venoms. Challenges were negative with sulfites, other additives and aging wines, but positive with young wines. Sera from all the patients detected Hymenoptera venom antigens. We report the first cases of sensitization to venom antigens by the oral route.

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[75] - Alfaya T, Ojeda P, Pineda F, Ojeda I, Ojeda J. Wine and hymenoptera venom allergy. Allergy 2009;64(Suppl. 90):238

Background: Wine allergy may be due to several chemical and biological wine components such as grape, fining agents (egg white, casein and isinglass), or tree nuts derived tannins. Recently, a relationship between wine and Hymenoptera venom allergy has been described. We describe a case of a patient with wine allergy who was also sensitized to Hymenoptera venom. Case report and methods: A 28 years old man developed generalized pruritus, facial angioedema, generalized urticaria, dyspnea and fainting, immediately after the intake of a white homemade Russian wine. Emergency treatment was required. Sometime later he tolerated other white and red commercial wines. No other food allergies were reported. He referred great local reaction after Hymenoptera sting. We performed skin prick tests with standard aeroallergens and foods, we measured specific IgE to food allergens and Hymenoptera venoms, and we performed SDS PAGE Immunoblotting with the culprit wine. Results: Skin prick tests with aeroallergens and food allergens were positive to Platanus pollen; grave, chestnut, peanut and pepper (although he usually tolerated these foods); and to Anisakis simplex. Skin prick test with the culprit wine was positive (three negative controls). Specific IgE was positive to Anisakis simplex, grape, pepper (class 2), chestnut, peanut (class 3) and to Apis mellifera (class 3) and Vespula sp. (class 2) venoms. Specific IgE to Polistes sp. venom was negative. SDS PAGE Immunoblotting to the culprit wine showed several binding bands around 10, 14.4, 18, 20-30, 45 and 97 kDa. Blotting inhibition, with wine in solid phase, showed that Apis mellifera venom inhibited a band around 14.4 kDa, whereas Vespula sp. and Polistes sp. venoms didn‚t show inhibition. Conclusion: We describe a serious, anaphylactic reaction after wine intake. We could establish cross reactivity among Apis mellifera venom and the culprit wine, so Apis mellifera venom contaminants in the wine could be responsible for the reaction. Wine allergy due to hymenoptera venom contaminants has been previously described, although the responsible venoms were from Vespula sp. or Polistes sp.

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[76] - Kanny G, Mouton C, Morisset M, Moneret-Vautrin DA. Food allergy to alcohol. Allergy 2003;58:535

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[77] - Sbornik M, Rakoski J, Mempel M, Ollert M, Ring J. IgE-mediated type-I-allergy against red wine and grapes. Allergy 2007;62:1339-1340

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[78] - Kanny G, Gerbaux V, Olszewski A, Frémont S, Empereur F, Nabet F, et al. No correlation between wine intolerance and histamine content of wine. J Allergy Clin Immunol 2001;107:375-378

BACKGROUND: Histamine is thought to be the main cause of adverse reactions to wines. OBJECTIVE: The purpose of this study was to test the hypothesis that the level of histamine in wine affects the tolerance to wine in 16 subjects with wine intolerance. METHODS: We performed a study to examine the effects of wine histamine content in 16 adults with wine intolerance. Each subject underwent 2 double-blind provocation tests with wine: 1 with a wine poor in histamine (0.4 mg/L), and 1 with a wine rich in histamine (13.8 mg/L). Blood was collected for histamine and methylhistamine RIAs at 0, 10, 30, and 45 minutes after ingestion of the wine. Methylhistamine and methylimidazolacetic acid (gas chromatography and mass spectrometry) were measured in urine 5 hours before and 5 hours after ingestion. RESULTS: No significant differences in the occurrence of adverse reactions were noted after ingestion of either of the wines (McNemar test). At 10 minutes, a significant increase was observed in plasma histamine with histamine-poor wine. No significant changes (Wilcoxon test) were observed in the methylhistamine and methylimidazolacetic acid levels after ingestion of either histamine-poor or histamine-rich wine. CONCLUSION: This study demonstrates that there is no correlation between the histamine content of wine and wine intolerance. The increase of plasma histamine levels at 10 minutes with histamine-poor wine suggested the role of a histamine-releasing substance. The role of acetaldehyde is discussed

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