Anaphylaxis and generalized urticaria from eating Chinese bayberry fruit

Anaphylaxis and generalized urticaria from eating Chinese bayberry fruit 1 first-author 2 corresp ‡Corresponding Author ‡Corresponding Author †E-mail:gaozhongshan@zju.edu.cn †E-mail:gaozhongshan@zju.edu.cn gaozhongshan@zju.edu.cn 2 1 1 3 4 Department of Allergy and Clinical Immunology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310013, China Department of Allergy and Clinical Immunology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310013, China Allergy Research Center, Department of Horticulture, College of Agriculture and Biotechnology, Zhejiang University, Hangzhou 310058, China Allergy Research Center, Department of Horticulture, College of Agriculture and Biotechnology, Zhejiang University, Hangzhou 310058, China Department of Clinic Laboratory, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310013, China Department of Clinic Laboratory, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310013, China Department of Experimental Immunology and Department of Otorhinolaryngology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, the Netherlands Department of Experimental Immunology and Department of Otorhinolaryngology, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, the Netherlands Chinese bayberry myrica rubra is a very popular fruit in southeastern China. In spite of its wide consumption, no allergies to this fruit have been reported previously. Here we report on a 40-year-old woman suffering from anaphylaxis to Chinese bayberry fruit. Prick-prick skin tests revealed strong reactions to fresh Chinese bayberry fruits as well as to peach, and weaker reactions to some other fruits including apple, melon, and banana. ImmunoCAP analysis revealed identical titers of specific IgE (4.3 kU A /L) to peach extract and its lipid transfer protein (LTP, rPru p 3), which was confirmed by detection of a 9 kD band following immunoblotting. Immunoblot analysis with Chinese bayberry extract gave bands of 22, 45, and 90 kD, but no 9 kD band was recognized. There was also no evidence of LTP recognition for loquat (36 kD) or melon (24 kD). This first report of a severe allergic reaction to Chinese bayberry fruit in a patient with LTP-mediated peach allergy indicates that other as yet unidentified non-pollen related fruit allergens are involved in this new severe fruit allergy. Chinese bayberry Fruit allergy Anaphylaxis Introduction 1 In China, fruit allergy is becoming a major health problem due to the dramatic increase in production and consumption of various fruits. The spread of local exotic fruits to a wider area may lead to the occurrence of previously unreported fruit allergies. Chinese bayberry ( myrica rubra ), belonging to the family Myricaceae and the order Fagales, is a native Chinese subtropical fruit with high anthocyanin content for which health promoting properties have been claimed (Chen et al., 2010 2010 ; Yang et al., 2011 2011 ; Zhang et al., 2011 2011 ). It is a very popular fruit consumed in China mostly fresh or as juice for more than 7 000 years (Xie et al., 2008 2008 ; Jiao et al., 2012 2012 ). In recent years its processed products have increasingly been exported to Europe and North America. In spite of its wide consumption, no allergies to this fruit have been reported previously. A native myrica cerifera bayberry (or wax-myrtle), within the same genus, has been reported as a tree pollen allergen source in USA (Prince and Meyer, 1977 1977 ). Since this genus belongs to the order Fagales to which birch trees also belong, the involvement of PR10 (Bet v 1-like) and/or profilin has been considered (Jacinto et al., 1992 1992 ). In this paper we report on a patient suffering anaphylaxis to Chinese bayberry together with mild allergy to other fruits. Case description 1 A 40-year-old Chinese woman received emergency treatment at the allergy department of our hospital after suffering anaphylaxis induced by eating Chinese bayberry fruit. The patient had no atopic family background and no history of rhino-conjunctivitis or asthma, but she had experienced episodes of food allergy as a young child. She claimed to have had allergic reactions to baby bok choy ( Brassica rapa var. Chinensis) as a very young child, as a consequence of which she avoided most vegetables and fruits. At ten years of age, she slowly started eating vegetables and fruits again, such as white Chinese cabbage and tomato, if no symptoms occurred. She continued to avoid banana and celery, because they induced severe oral allergy syndrome (OAS). Apple, peach, loquat, and Chinese bayberry were tolerated until three years ago when she experienced an episode of systemic urticaria within 5 min after eating peach and Chinese bayberry fruit. She also then felt uncomfortable eating apple, plum, loquat, banana, and melon, but tolerated watermelon and kiwi. During the same period, washing rice resulted in contact urticaria on her hands and eyelids. One year later, trying one Chinese bayberry again, she developed anaphylaxis that was resolved only after emergency treatment. On that occasion, skin prick tests for reaction to mites, molds, mixed pollen, and animal dander were all negative (ALK-Abelló A/S, Horsholm, Denmark). One year later, this patient was enrolled for further skin test studies and serum IgE analysis. Strong positive skin tests were observed with two Chinese bayberry fruit cultivars (‘Shuijing’ and ‘Dongkui’) and peach extract. She also showed a mild reaction to fresh peach, apple, and melon fruits and washing water of rice, as well as Chinese bayberry juice, but not bayberry extract (Table 1 1 ). Specific IgE measurements by ImmunoCAP (Thermo-Fisher, Uppsala, Sweden) revealed an elevated total serum IgE (451.4 kU A /L), and specific IgE titers against peach, melon, and mugwort pollen extract of 4.3, 0.7, and 1.2 kU A /L, respectively. Single component ImmunoCAP analysis demonstrated specific IgE against rPru p 3 was 4.3 kU A /L and nArt v 3 IgE was 0.4 kU A /L. rPru p 1 (Bet v 1 homologue), rPru p 4 (profilin), and rArt v 1 IgE were negative ( < 0.35 kU A /L) (peach and mugwort sIgE data are from patient S24 reported by Gao et al. ( 2012 2012 )). Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE)/immunoblotting with protein extracts from peach fruit peel (cv. ‘Yulu’), Chinese bayberry whole fruit ( Myrica rubra cv. ‘Biqi’), loquat peel ( Eriobotrya japonica cv. ‘Ninghaibai’), and melon flesh was carried out to investigate which individual allergens may be involved in the reactions to Chinese bayberry and other fruits. With peach, a putative LTP band at 9 kD was detected, which is in agreement with the positive rPru p 3 CAP result. Surprisingly, with Chinese bayberry there was no recognition of a 9-kD LTP band, but instead three as yet unidentified bands were found at 22, 45 and 90 kD, indicating that the bayberry allergy of this patient is not a cross-reactive phenomenon induced by Pru p 3 primary sensitization. With loquat a 36-kD band was detected, and with melon, a 24-kD band (Fig. 1 1 ). Written consent was obtained from the patient and this study was approved by the local ethics committee (authorization No. 2011-R-1, the Second Affiliated Hospital, School of Medicine, Zhejiang University, China). Allergen source Wheal size (mm) Times of the positive control Chinese bayberry cv. Shuijing 15×11 3.44 Chinese bayberry cv. Dongkui 13×11 2.98 Chinese bayberry cv. Biqi 11×7 1.60 Chinese bayberry juice 12×4 1.00 Peach 10×6 1.25 Melon 15×5 1.56 Apple cv. Fuji 8×8 1.33 Banana 6×5 0.63 Litchi 3×3 0.19 Rice washing water 14×8 2.12 Peach extract, 400 μg/ml 18×20 7.50 Peach extract, 40 μg/ml 15×14 4.58 Peach extract, 4 μg/ml 17×10 3.14 Chinese bayberry extract, 25 μg/ml 3×3 0.19 Histamine, 10 mg/ml 8×6 1.00 Negative control (Saline) 0 (a) SDS-PAGE of protein extracts from fruits; (b) Immunoblots with the patient serum. M: protein molecular weight marker in kD (invitrogen LC5800); 1: peach (cv. Yulu, peel); 2: Chinese bayberry ( Myrica rubra cv. Biqi, whole fruit); 3: Loquat ( Eriobotrya japonica cv. Ninghaibai, peel); 4: melon flesh Discussion 1 In Europe, fresh fruits have been found to be the most frequent cause of food allergies in patients over five years of age (Fernández-Rivas et al., 2008 2008 ). Usually these allergies are considered to result from primary sensitization to pollen or latex, but peach LTP has been described as the primary sensitizer responsible for often severe peach allergy and cross-reactivity to other fruits and vegetables and even to pollen (Rossi et al., 2009 2009 ; Schulten et al., 2011 2011 ). Peach allergy patients in China have been classified into two groups: a larger group frequently reported in north China resulting from high exposure and strong sensitization to mugwort pollen LTP, and a smaller group in south China resulting from peach fruit LTP sensitization (Gao et al., 2012 2012 ). This case belongs to the south China peach allergy group, but there was no evidence of LTP recognition with Chinese bayberry, loquat or melon fruit extracts. From an “expressed-sequence tag” (EST) survey of bayberry fruit, it was found that the fruit contains at least two isoforms of LTP, a longer one with 66.3% amino acid identity to Pru p 3.01 and a shorter one with 29.5% identity. Neither appears to be recognized by cross-reactive Pru p 3 specific IgE. Negative single component Pru p 1 and Pru p 4 CAP and immunoblot results suggested that PR-10 (Bet v 1 homologues) and profilin are also not the allergens for this patient. One of the identified bands of 22 kD corresponds to the molecular weight ( M W ) of the reported fruit allergen thaumatin-like protein (TLP) (Breiteneder, 2004 2004 ). The fact that its putative encoding gene is abundantly expressed during bayberry fruit ripening (unpublished data) warrants further studies into a possible role for a TLP in the bayberry fruit allergy. With preliminary skin prick tests showing possible allergenicity differences among Chinese bayberry cultivars (Table 1 1 ), further in vitro and in vivo testings with more patients and cultivars are planned to select hypoallergenic cultivars using similar approaches to that used in apple (Gao and Gilissen, 2011 2011 ). In conclusion, to the best of our knowledge, this is the first case report of severe allergy to Chinese bayberry. Further molecular characterization of the allergens involved in the allergy to this exotic fruit is needed. Research on other fruit TLP allergens provides useful references (Gavrović-Jankulović et al., 2002 2002 ; Breiteneder, 2004 2004 ). References H Breiteneder . Thaumatin-like proteins—a new family of pollen and fruit allergens . Allergy , 2004 . 59 ( 5 ): 479 - 481 . 15080826 DOI: 10.1046/j.1398-9995.2003.00421.x http://doi.org/10.1046/j.1398-9995.2003.00421.x . Thaumatin-like proteins—a new family of pollen and fruit allergens K Chen , C Xu , B Zhang , 等 . J Janick . Red Bayberry: Botany and Horticulture . Horticultural Reviews , 2010 . : Oxford, UK John Wiley & Sons Inc , 83 - 114 . DOI: 10.1002/9780470650837.ch3 http://doi.org/10.1002/9780470650837.ch3 . Red Bayberry: Botany and Horticulture M Fernández-Rivas , C Benito , E Gonzalez-Mancebo , M de Durana . Allergies to fruits and vegetables . Pediatr Allergy Immunol , 2008 . 19 ( 8 ): 675 - 681 . 19097271 DOI: 10.1111/j.1399-3038.2008.00821.x http://doi.org/10.1111/j.1399-3038.2008.00821.x . Allergies to fruits and vegetables ZS Gao , LJWJ Gilissen . MA Jenks , PJ Bebeli . Breeding of Hypoallergenic Fruits . Breeding for Fruit Quality , 2011 . : Oxford, UK John Wiley & Sons Inc , 105 - 126 . DOI: 10.1002/9780470959350.ch5 http://doi.org/10.1002/9780470959350.ch5 . Breeding of Hypoallergenic Fruits ZS Gao , ZW Yang , SD Wu , HY Wang , ML Liu , WL Mao , J Wang , G Gadermaier , F Ferreira , M Zheng , 等 . Peach allergy in China: a dominant role for mugwort pollen lipid transfer protein as a primary sensitizer . J Allergy Clin Immunol , 2012 . in press DOI: 10.1016/j.jaci.2012.07.015 http://doi.org/10.1016/j.jaci.2012.07.015 . Peach allergy in China: a dominant role for mugwort pollen lipid transfer protein as a primary sensitizer M Gavrović-Jankulović , T Cirkovic , O Vuckovic , M Atanaskovic-Markovic , A Petersen , G Gojgic , L Burazer , RM Jankov . Isolation and biochemical characterization of a thaumatin-like kiwi allergen . J Allergy Clin Immunol , 2002 . 110 ( 5 ): 805 - 810 . 12417892 DOI: 10.1067/mai.2002.128947 http://doi.org/10.1067/mai.2002.128947 . Isolation and biochemical characterization of a thaumatin-like kiwi allergen CM Jacinto , RP Nelson , GA Bucholtz , E Fernandez-Caldas , WL Trudeau , RF Lockey . Nasal and bronchial provocation challenges with bayberry ( Myrica cerifera ) pollen extract . J Allergy Clin Immunol , 1992 . 90 ( 3 ): 312 - 318 . 1527315 DOI: 10.1016/S0091-6749(05)80008-9 http://doi.org/10.1016/S0091-6749(05)80008-9 . Nasal and bronchial provocation challenges with bayberry (Myrica cerifera) pollen extract Y Jiao , HM Jia , XW Li , ML Chai , HJ Jia , Z Chen , GY Wang , CY Chai , EW van de Weng , ZS Gao . Development of simple sequence repeat (SSR) markers from a genome survery of Chinese bayberry ( Myrica rubra ) . BMC Genomics , 2012 . 13 ( 1 ): 201 DOI: 10.1186/1471-2164-13-201 http://doi.org/10.1186/1471-2164-13-201 . Development of simple sequence repeat (SSR) markers from a genome survery of Chinese bayberry (Myrica rubra) HE Prince , GH Meyer . Hay fever from southern wax-myrtle ( Myrica cerifera ): a case report . Ann Allergy , 1977 . 38 ( 4 ): 252 - 254 . 557937 . Hay fever from southern wax-myrtle (Myrica cerifera): a case report RE Rossi , G Monasterolo , GW Canonica , G Passalacqua . Systemic reactions to peach are associated with high levels of specific IgE to Pru p 3 . Allergy , 2009 . 64 ( 12 ): 1795 - 1796 . 19732048 DOI: 10.1111/j.1398-9995.2009.02133.x http://doi.org/10.1111/j.1398-9995.2009.02133.x . Systemic reactions to peach are associated with high levels of specific IgE to Pru p 3 V Schulten , B Nagl , E Scala , ML Bernardi , A Mari , MA Ciardiello , I Lauer , S Scheurer , P Briza , A Jurets , 等 . Pru p 3, the nonspecific lipid transfer protein from peach, dominates the immune response to its homolog in hazelnut . Allergy , 2011 . 66 ( 8 ): 1005 - 1013 . 21352239 DOI: 10.1111/j.1398-9995.2011.02567.x http://doi.org/10.1111/j.1398-9995.2011.02567.x . Pru p 3, the nonspecific lipid transfer protein from peach, dominates the immune response to its homolog in hazelnut LJ Xie , XQ Ye , DH Liu , YB Ying . Application of principal component-radial basis function neural networks (PC-RBFNN) for the detection of water-adulterated bayberry juice by near-infrared spectroscopy . J Zhejiang Univ-Sci B , 2008 . 9 ( 12 ): 982 - 989 . 19067467 DOI: 10.1631/jzus.B0820057 http://doi.org/10.1631/jzus.B0820057 . Application of principal component-radial basis function neural networks (PC-RBFNN) for the detection of water-adulterated bayberry juice by near-infrared spectroscopy Z Yang , S Cao , Y Zheng . Chinese bayberry fruit extract alleviates oxidative stress and prevents 1,2-dimethylhydrazine-induced aberrant crypt foci development in rat colon carcinogenesis . Food Chem , 2011 . 125 ( 2 ): 701 - 705 . DOI: 10.1016/j.foodchem.2010.09.070 http://doi.org/10.1016/j.foodchem.2010.09.070 . Chinese bayberry fruit extract alleviates oxidative stress and prevents 1,2-dimethylhydrazine-induced aberrant crypt foci development in rat colon carcinogenesis B Zhang , M Kang , Q Xie , B Xu , C Sun , K Chen , Y Wu . Anthocyanins from Chinese bayberry extract protect β cells from oxidative stress-mediated injury via HO-1 upregulation . J Agric Food Chem , 2011 . 59 ( 2 ): 537 - 545 . 21166417 DOI: 10.1021/jf1035405 http://doi.org/10.1021/jf1035405 . Anthocyanins from Chinese bayberry extract protect β cells from oxidative stress-mediated injury via HO-1 upregulation 10.1631/jzus.B1200150 Project (Nos. 30971970 and 30600266) supported by the National Natural Science Foundation of China 2012-05-21 2012-09-19 2012-09-03 2022-01-05 Copyright © Zhejiang University and Springer-Verlag Berlin Heidelberg 2012 2012 Journal of Zhejiang University-SCIENCE B (Biomedicine and Biotechnology) 10 13