DFG VCH. Deutsche Forschungsgemeinschaft. Food Allergies and Intolerances. Symposium

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1 Deutsche Forschungsgemeinschaft Food Allergies and Intolerances Symposium Editors: Gerhard Eisenbrand (Chairman, Senate Commission on the Evaluation of Food Safety), Holger Aulepp, Anthony David Dayan, Peter Stefan Elias, Werner Grunow, Johannes Ring, Josef Schlauer Scientific Secretariate: Werner Kohl, Matthias Baum VCH DFG

2 Vorwort Preface XV XVII Part A I Zusammenfassungen 3 1 Epidemiologie der Allergien und Intoleranzen durch Lebensmittel und Lebensmitteladditiva: das Problem der Validität der Daten 3 Brunello Wüthrich 2 Epidemiologie von Lebensmittelallergien 4 Torsten Schäfer und Johannes Ring 3 Klassifizierung nahrungsmittelbedingter Unverträglichkeitsreaktionen 5 Johannes Ring 4 Methoden zur Erfassung von lebensmittelbedingten Allergien 6 Jürgen Knop und Joachim Saloga 5 Lebensmittelallergie - der Weg der Sensibilisierung und seine Bedeutung für die Risikoeinschätzung 8 Charlotte Madsen 6 MHC-Moleküle und Antigenprozessierung 9 Hans-Georg Rammensee 7 Strategien einer prospektiven Allergenizitätstestung.. 10 Andreas Radbruch 8 Molekulare Grundlagen der Allergencharakterisierung. 11 Kjell Aas V

3 9 C h a r a k t e r i s i e r u n g v o n p f l a n z l i c h e n A l l e r g e n e n Wolt-Meinhard Becker 10 Labile und stabile Allergene in pflanzlichen Lebensmitteln 13 Stefan Vieths, Holger Aulepp, Wolf-Meinhard Becker und Lieselotte Buschmann 11 Mikrobielle Allergene 14 Martin Schata 12 Allergene Proteine im Reis: Strategien zur Verminderung und Bewertung 14 Tsukasa Matsuda, Masahiro Nakase, Takahiro Adachi, Ryo Nakamura, Yuichi Tada, Hiroaki Shimada, Masayoshi Takahashi und Tatsuhito Fujimura 13 Transgene Fische: Stand der Forschung 15 Thomas T. Chen 14 Bewertung der Allergenität von Lebensmittelproteinen. 16 Geert F. Houben und Andre H. Penninks 15 Transgene Sojabohnen mit Paranuß 2S Speicherprotein: Aspekte möglicher Allergierisiken 17 J. A. Nordlee, S. L. Taylor, J. A. Townsend, L. A. Thomas und Larry R. Beach 16 Sicherheitsstrategien hinsichtlich Allergie durch bioindustrielle Enzyme in der Lebensmittelherstellung Torben B. S0rensen 17 Allergenes Potential von gentechnisch veränderten Pflanzen 18 Roy L. Fuchs II Hauptschlußfolgerungen und Empfehlungen 20 Part B I Clinical Aspects, Epidemiology, Validity of Data Epidemiology of Allergies and Intolerances Caused by Foods and Food Additives: The Problem of Data Validity. 31 Brunello Wüthrich 1.1 Abstract Introduction Definition of adverse reactions to food 33 VI

4 1.4 Symptoms of food allergy Prevalence of adverse reactions to food The problem of data validity Conclusion References 38 2 Epidemiology of Adverse Food Reactions Due to Allergy or Other Forms of Hypersensitivity 40 Torsten Schäfer and Johannes Ring 2.1 Abstract Introduction Definitions Epidemiological methodology Allergen sources - quantity and quality Frequency of food allergies in general population Studies using questionnaire, skin prick test and/or RAST Studies using oral provocation tests Own results Associations of adverse food reactions (allergy/hypersensitivity) Association with age and natural course Association with gender Adjuvant factors Allergen avoidance Prevention of food allergy Conclusion References 53 3 Classification of Adverse Food Reactions 55 Johannes Ring 3.1 Abstract Introduction Clinical symptomatology Urticaria and angioedema Anaphylaxis and anaphylactoid reactions Atopic eczema Allergie contact eczema Photosensitization Gastroenteritis Gluten-sensitive enteropathy and dermatitis herpetiformis (Duhring) Allergie (leucocytoclastic) vasculitis Eco-syndrome (clinical ecology syndrome) Pathophysiology 59 VII

5 3.5 Allergie reactions Mechanisms of sensitization Idiosyncrasy/Pseudo-allergy Eliciting substances of adverse food reactions Conclusion References 62 4 Discussion of Methods for Detection of Food Allergies.. 65 Jürgen Knop and Joachim Saloga 4.1 Abstract Introduction Clinical history In vitro tests Skin tests Elimination diets Food challenge Conclusion and future directions References 73 5 Allergy to Food - The Significance of Route of Sensitization to Risk Assessment 75 Charlotte Madsen 5.1 Abstract Introduction Sensitization in humans younger than two years of age Sensitization in humans older than two years of age Contact allergens Conclusion References 79 II Molecular Basis of Allergenicity and Allergen Characterization 81 6 Physiological Function of MHC Moleeules 81 Hans-Georg Rammensee 6.1 Abstract Introduction Peptide ligands of MHC dass I moleeules Peptide ligands of MHC dass II moleeules Conclusion Further reading ' 100 VIII

6 7 Strategies for Prospective Testing 101 Andreas Radbruch 7.1 Abstract Introduction Processing and presentation of antigen: the genetic basis of immune responsiveness Choice of immune response: inflammation versus allergy Setup and evaluation of in vitro immune reactions A prospective in vitro test System References Molecular Basis of Allergen Charaeterization 108 Kjell Aas 8.1 Abstract Allergy Allergy immunology Allergy in biology and experiments Food allergens Immunogenicity and antigenicity Allergenic potency Major, intermediate and minor allergens Denaturation Epitopes Epitope strueture The mast cell amplifier Immunogenicity and allergenicity Allergen charaeterization IgE preference? Allergen research Isoallergens A model in epitope research Allergen research depends on appropriate patients Allergen M in codfish Several epitopes reacting with same or different antibodies Allergenic epitope strueture Modern techniques Monoclonal antibodies and DNA recombinant techniques References Characterization of Allergens from Plants 119 Wolf-Meinhard Becker 9.1 Abstract Introduction Definition of allergens 119 IX

7 9.2.2 Issues of allergen characterization Line of approach to characterize allergens Separation techniques in allergen characterization and their combination with immunological methods Electrophoretic Separation methods Transfermembranes Blotting methods IEF/SDS-PAGE/2-D electrophoresis/immunoblotting Immunological tools to identify and quantify allergens Chemical methods to characterize allergens Strategies of molecular cloning of allergens Isolation of mrna from the allergenic source Preparing and immunoscreening a cdna library Conclusion References Characterization of Labile and Stable Allergens in Foods of Plant Origin 130 Stefan Vieths, Holger Aulepp, Wolf-Meinhard Becker and Lieselotte Buschmann 10.1 Abstract Introduction Subject Terms Allergenicity of processed plant foods Plant food allergies "Classical" food allergies Pollen related food allergies Food allergy and cross-reactivity Characteristics of important plant food allergens Profilins The major apple allergen Mal d 1 and other plant food allergens of the "Bet v 1-family" Celery Peanut Concluding remarks Acknowledgements References Allergens from Microorganisms 150 Martin Schata 11.1 Abstract Introduction The biology and classification of moulds 153

8 11.4 Occurrence of moulds in different environments Food contamination and fungal enzymes in food engineering Characterized allergens of moulds References 159 III The Input of Molecular Biology: Transgenic Foods Allergenic Proteins in Rice: Strategies for Reduction and Evaluation 161 Tsukasa Matsuda, Masahiro Nakase, Takahiro Adachi, Ryo Nakamura, Yuichi Tada, Hiroaki Shimada, Masayoshi Takahashi and Tatsuhito Fujimura 12.1 Abstract Allergenic proteins in rice Cloning of rice allergen genes cdna cloning and deduced amino acid sequences of rice allergens Cloning of rice allergen genomic DNA Repression of allergen expression by antisense RNA Construction of antisense allergen genes Introduction of antisense allergen genes into rice Allergen analyses for transgenic rice plants The transmission and expression of the introduced antisense gene among the transformant progeny Acknowledgement References, Current Status of the Transgenic Fish Research Thomas T. Chen 13.1 Abstract Introduction Growth promoting effects of recombinant growth hormone Production of transgenic fish Gene transfer method Identification and characterization of transgenic fish Growth hormone and insulin-like growth factor transgenic fish Other transgenic fish Applications and perspectives References 180 XI

9 IV Strategies of Safety Evaluation Evaluation of the Allergenicity of Food Proteins - Current Testing Possibilities and New Developments Focused on the Role of the Gastro-Intestinal Tract Physiology Geert F. Houben and Andre H. Penninks 14.1 Abstract Introduction: adverse reactions to food Mechanisms of allergy The atopic syndrome and IgE-mediated (food) allergy Food allergens Modification of the allergenicity of dietary proteins Novel foods and novel food ingredients Current testing possibilities for the evaluation of the allergenicity of food proteins In vivo antigenicity assays Physico-chemical and immunochemical analyses Mast cell and basophile degranulation tests The role of the gastro-intestinal tract physiology in food allergy New approaches in food allergy research and allergenicity testing: the role of the gastro-intestinal tract physiology Gastro-intestinal digestion modelling Intestinal epithelial passage modelling A refined approach in food allergenicity research References Transgenic Soybeans Containing Brazil Nut 2S Storage Protein: Issues Regarding Allergenicity 196 J. A. Nordlee, S. L. Taylor, J. A. Townsend, L. A. Thomas and Larry R. Beach 15.1 Abstract Introduction Materials and methods Sera Seeds and proteins RAST inhibition Immunoblotting Results RAST inhibition SDS-PAGE Immunoblotting Discussion References 201 XII

10 16 Safety Strategies Regarding Allergy to Bioindustrial Enzymes in Food-Processing 203 Torben B. Serensen 16.1 Abstract Introduction The use of enzymes in food processing Production of bioindustrial enzymes Applications and types of enzymes Safety assessment strategy Inborn product safety; microorganisms, enzyme products Genetically modified organisms for production of enzymes Allergy Enzyme products Applications Possible risk groups Surveillance of adverse reactions Conclusion References Assessment of the Allergenic Potential of Foods Derived from Genetically Engineered Plants: Glyphosate Tolerant Soybean as a Case Study 212 Roy L. Fuchs 17.1 Abstract Introduction The source Host Introduced protein(s) References 219 Main Conclusions and Recommendations 223 Authors' Addresses 231 XIII