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Molecular Allergy Diagnostics

E-BookPDF1 - PDF WatermarkE-Book
531 Seiten
Englisch
Springer International Publishingerschienen am08.05.20171st ed. 2017
This book, based on a recent German publication, offers an overview of basic data and recent developments in the groundbreaking field of molecular allergology. It comprehensively explores the origin and structure of single allergen molecules ('components') and their utility in improving the management of type I, IgE-mediated allergic reactions and disorders like allergic respiratory diseases, food allergies, and anaphylaxis. 

Highly specific testing, called component-resolved diagnostics, aims to identify and utilize single molecules. Over 200 single allergens from plant or animal sources have been applied to single or multiplex laboratory testing for the presence of allergen-specific IgE. This leap in assay sensitivity and specificity has led to three major advances in patient management: discrimination between primary allergic sensitization and complex cross-reactivity, recognition of IgE profiles for certain allergens and identification of patients most likely to benefit from allergen-specific immunotherapy. 

The book discusses in detail the benefits and limitations of this 21st century technology, and offers suggestions for the use of molecular allergology in routine clinical practice. It is a 'must read' for physicians treating allergic patients as well as scientists interested in natural allergic molecules and their interactions with the human immune system.



Thilo Jakob is Professor for Dermatology and Allergology at the Medical Faculty, Justus-Liebig-University in Gießen, and Chair of the Department of Dermatology and Allergology at the University Medical Center Giessen and Marburg (UKGM), Campus Giessen, Germany. He trained with Prof. Ivan Roitt, University College, London, Dres Steven Katz and Mark Udey, N.I.H. Bethesda, USA, and Prof. Johannes Ring, Technische Universität Munich, Germany. His research interests are focused on clinical and experimental allergology and immunodermatology, related to which he has published 110 original articles, with a cumulative impact factor of 672, over 3000 citations, 97 reviews and book chapters. He was awarded numerous research and teaching prizes such as the University Teaching Award in 2010 and the e-learing Award by the Albert Ludwigs University Freiburg in 2013. He is currently board member of the Executive Committee of the German Society of Allergy and Clinical Immunology (DGAKI), past member of the Executive Committee European Academy of Allergy and Clinical Immunology (2005-2009) and past Chairman of the  Immunology Section of the EAACI. He is currently the Editor in Chief of the Allergo Journal International, the official journal of the German Society of Allergy and Clinical Immunology and the Medical Association of German Allergist (since 2010), Associate Editor of International Archives of Allergy and Immunology and serves on the editorial board of a number of allergy and dermatology journals.

Jörg Kleine-Tebbe is working as an allergist and dermatologist at the Allergy and Asthma Center Westend, Berlin, a private practice and research center. After the MD in medicine, he earned a Clinical and Research Fellowship at the Asthma OPD and Department of Clinical Immunology (Chair: Prof. Dr. Gert Kunkel), University Hospital Rudolf Virchow, Freie Universität Berlin, Germany. He continued with allergy & immunology related basic research (Visiting Instructor in Medicine) at the Johns Hopkins Asthma & Allergy Center, Allergy and Clinical Immunology Division (L. M. Lichtenstein, D. G. Marsh), Baltimore MD, USA. Afterwards he became Senior Resident and Instructor at the University Dermatology Hospital in Leipzig. Later he transferred his habilitation and lectureship to the Charité, Berlin (University Hospital of Dermatology and Allergology, Humboldt University) and, successively, joined the team of Prof. Dr. Gert Kunkel, at Allergy and Asthma Center Westend (AAZW), a Multi-Group Private Practice for Allergology, Internal Medicine and Dermatology with an integrated Clinical Research Center (UZDAA) for Allergology, Airway & Lung Diseases and Dermatology. Jörg Kleine-Tebbe has authored and co-authored numerous national and international guidelines and has been Chairman of the EAACI Interest Group Allergy Diagnosis, is currently Board Member of the EAACI Interest Group Immunotherapy, member of the AAAAI Immunotherapy, Allergen Standardization and Allergy Diagnostics Committee and the AAAAI Practice, Diagnostics and Therapeutics Committee and Executive Committee member of the German Society of Allergy and clinical Immunology (DGAKI). 


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Produkt

KlappentextThis book, based on a recent German publication, offers an overview of basic data and recent developments in the groundbreaking field of molecular allergology. It comprehensively explores the origin and structure of single allergen molecules ('components') and their utility in improving the management of type I, IgE-mediated allergic reactions and disorders like allergic respiratory diseases, food allergies, and anaphylaxis. 

Highly specific testing, called component-resolved diagnostics, aims to identify and utilize single molecules. Over 200 single allergens from plant or animal sources have been applied to single or multiplex laboratory testing for the presence of allergen-specific IgE. This leap in assay sensitivity and specificity has led to three major advances in patient management: discrimination between primary allergic sensitization and complex cross-reactivity, recognition of IgE profiles for certain allergens and identification of patients most likely to benefit from allergen-specific immunotherapy. 

The book discusses in detail the benefits and limitations of this 21st century technology, and offers suggestions for the use of molecular allergology in routine clinical practice. It is a 'must read' for physicians treating allergic patients as well as scientists interested in natural allergic molecules and their interactions with the human immune system.



Thilo Jakob is Professor for Dermatology and Allergology at the Medical Faculty, Justus-Liebig-University in Gießen, and Chair of the Department of Dermatology and Allergology at the University Medical Center Giessen and Marburg (UKGM), Campus Giessen, Germany. He trained with Prof. Ivan Roitt, University College, London, Dres Steven Katz and Mark Udey, N.I.H. Bethesda, USA, and Prof. Johannes Ring, Technische Universität Munich, Germany. His research interests are focused on clinical and experimental allergology and immunodermatology, related to which he has published 110 original articles, with a cumulative impact factor of 672, over 3000 citations, 97 reviews and book chapters. He was awarded numerous research and teaching prizes such as the University Teaching Award in 2010 and the e-learing Award by the Albert Ludwigs University Freiburg in 2013. He is currently board member of the Executive Committee of the German Society of Allergy and Clinical Immunology (DGAKI), past member of the Executive Committee European Academy of Allergy and Clinical Immunology (2005-2009) and past Chairman of the  Immunology Section of the EAACI. He is currently the Editor in Chief of the Allergo Journal International, the official journal of the German Society of Allergy and Clinical Immunology and the Medical Association of German Allergist (since 2010), Associate Editor of International Archives of Allergy and Immunology and serves on the editorial board of a number of allergy and dermatology journals.

Jörg Kleine-Tebbe is working as an allergist and dermatologist at the Allergy and Asthma Center Westend, Berlin, a private practice and research center. After the MD in medicine, he earned a Clinical and Research Fellowship at the Asthma OPD and Department of Clinical Immunology (Chair: Prof. Dr. Gert Kunkel), University Hospital Rudolf Virchow, Freie Universität Berlin, Germany. He continued with allergy & immunology related basic research (Visiting Instructor in Medicine) at the Johns Hopkins Asthma & Allergy Center, Allergy and Clinical Immunology Division (L. M. Lichtenstein, D. G. Marsh), Baltimore MD, USA. Afterwards he became Senior Resident and Instructor at the University Dermatology Hospital in Leipzig. Later he transferred his habilitation and lectureship to the Charité, Berlin (University Hospital of Dermatology and Allergology, Humboldt University) and, successively, joined the team of Prof. Dr. Gert Kunkel, at Allergy and Asthma Center Westend (AAZW), a Multi-Group Private Practice for Allergology, Internal Medicine and Dermatology with an integrated Clinical Research Center (UZDAA) for Allergology, Airway & Lung Diseases and Dermatology. Jörg Kleine-Tebbe has authored and co-authored numerous national and international guidelines and has been Chairman of the EAACI Interest Group Allergy Diagnosis, is currently Board Member of the EAACI Interest Group Immunotherapy, member of the AAAAI Immunotherapy, Allergen Standardization and Allergy Diagnostics Committee and the AAAAI Practice, Diagnostics and Therapeutics Committee and Executive Committee member of the German Society of Allergy and clinical Immunology (DGAKI). 


Details
Weitere ISBN/GTIN9783319424996
ProduktartE-Book
EinbandartE-Book
FormatPDF
Format Hinweis1 - PDF Watermark
FormatE107
Erscheinungsjahr2017
Erscheinungsdatum08.05.2017
Auflage1st ed. 2017
Seiten531 Seiten
SpracheEnglisch
IllustrationenXX, 531 p. 112 illus., 100 illus. in color.
Artikel-Nr.2377850
Rubriken
Genre9200

Inhalt/Kritik

Inhaltsverzeichnis
1;Foreword 1;5
2;Foreword 2;7
3;Preface;9
3.1;Molecular Allergology: From Research Topic to Innovative Allergy Diagnosis;9
4;Acknowledgments;11
5;Contributors;16
6;Contents;13
7;Part I: Protein Families and Relationships;20
7.1;1: Introduction to Molecular Allergology: Protein Families, Databases, and Potential Benefits;21
7.1.1;1.1 The Era of Molecular Allergology;22
7.1.2;1.2 Immediate-Type Allergens and Their Names;23
7.1.3;1.3 Sequence and Structure: From T Cell to Antibody (B Cell) Epitopes;24
7.1.4;1.4 Protein Families and Relatedness of Type I Allergens;24
7.1.5;1.5 Databases for Clinical Practice and Research;27
7.1.6;1.6 Potential Use of Single Allergens;30
7.1.6.1;1.6.1 Quantification of Allergens in Extracts;30
7.1.6.2;1.6.2 Molecular Epidemiology;31
7.1.6.3;1.6.3 Diagnostics with Single Allergens;31
7.1.7;1.7 Scope and Limits of Interpretation;33
7.1.8;1.8 Immunotherapy and Single Allergens;33
7.1.9;1.9 Molecular Allergology Drives Innovation;34
7.1.10; Conclusions;35
7.1.11;References;35
7.2;2: Bet v 1 and its Homologs: Triggers of Tree-Pollen Allergy and Birch Pollen-­Associated Cross-Reactions;38
7.2.1;2.1 Introduction;38
7.2.2;2.2 Biological Facts and Characteristics;39
7.2.2.1;2.2.1 Allergen Identification;39
7.2.2.2;2.2.2 Family;39
7.2.2.3;2.2.3 Bet v 1 and the Bet v 1 Superfamily;39
7.2.2.4;2.2.4 Physiological Function of Bet v 1;40
7.2.2.5;2.2.5 Characteristics;41
7.2.3;2.3 Importance of Bet v 1 and Related Allergens;41
7.2.3.1;2.3.1 Sources of Bet v 1 and its Biological and Allergological Role;41
7.2.3.2;2.3.2 Prevalence and Distribution of Sensitization;42
7.2.3.3;2.3.3 Bet v 1: A Marker Allergen for Tree (Fagales Order) Pollen Sensitization and IgE Cross-Reactivity to Plant-Derived Foods;42
7.2.3.3.1;2.3.3.1 Bet v 1 Cross-Reactive Inhalant Allergens;42
7.2.3.3.2;2.3.3.2 Bet v 1 Cross-Reactive Food Allergens;43
7.2.4;2.4 Diagnosis;45
7.2.4.1;2.4.1 Airway Symptoms Caused by Tree Pollen Allergy;45
7.2.4.2;2.4.2 Bet v 1-Associated Cross-Allergies to Plant-Derived Foods;47
7.2.4.3;2.4.3 Added Benefits of Molecular Diagnostics;54
7.2.4.3.1;2.4.3.1 Advantages of Bet v 1 in Molecular Diagnostics;55
7.2.4.3.2;2.4.3.2 Possibilities of Diagnostics Using Bet v 1-Homologous Allergens;55
7.2.5;2.5 Therapy and Recommendations;57
7.2.6;2.6 Perspectives;57
7.2.7;2.7 Conclusions for Clinical Practice;57
7.2.8;References;57
7.3;3: The Concept of Pollen Panallergens: Profilins and Polcalcins;60
7.3.1;3.1 Introduction;60
7.3.2;3.2 Allergen Nomenclature;61
7.3.3;3.3 Structure and Function of Profilins;61
7.3.4;3.4 Relevance of Profilins;63
7.3.5;3.5 Sensitization to Profilins;64
7.3.6;3.6 Structure and Function of Polcalcins;65
7.3.7;3.7 Relevance of Polcalcins;65
7.3.8;3.8 Diagnosis of Relevant Multi-Sensitizations to Pollen;66
7.3.9;3.9 Component-Resolved Diagnosis of Panallergen Sensitizations;68
7.3.10;3.10 Clinical Relevance of Panallergens;68
7.3.11;3.11 Extract Selection for Allergen Immunotherapy (AIT);70
7.3.12;3.12 Conclusions from a Clinical Perspective;71
7.3.13;References;71
7.4;4: Stable Plant Food Allergens I: Lipid-Transfer Proteins;74
7.4.1;4.1 Introduction;74
7.4.2;4.2 Structure of Allergens;75
7.4.3;4.3 Biological Function of Allergens;77
7.4.4;4.4 Frequency of Sensitization and Geographic Distribution;77
7.4.5;4.5 Clinical Relevance;80
7.4.6;4.6 IgE Cross-Reactivity Between LTPs;81
7.4.7;4.7 Diagnosis by Sensitization Tests with LTPs and LTP-­Containing Extracts;84
7.4.8;4.8 Clinical Relevance of LTP Sensitization;85
7.4.9;4.9 Therapeutic Recommendations;87
7.4.10;4.10 Other Perspectives;87
7.4.11;4.11 Implications for Routine Clinical Practice;87
7.4.12;References;88
7.5;5: Stable Plant Food Allergens II: Storage Proteins;93
7.5.1;5.1 Introduction;93
7.5.2;5.2 Allergen Nomenclature;94
7.5.3;5.3 Protein Structures;94
7.5.4;5.4 Functions;97
7.5.5;5.5 Relevance;98
7.5.6;5.6 Complex Cross-Reactivity Among Storage Proteins;98
7.5.7;5.7 Diagnostic Challenges;101
7.5.8;5.8 Additional Possible Benefits from Molecular Diagnostics;102
7.5.9;5.9 Outlook;104
7.5.10;5.10 Conclusion: Potential for Routine Clinical Practice;104
7.5.11;References;104
7.6;6: Cross-Reactive Carbohydrate Determinants: Diagnostic and Clinical Relevance;107
7.6.1;6.1 Introduction;108
7.6.1.1;6.1.1 Cross-Reactive Carbohydrate Determinants;109
7.6.2;6.2 Allergen Sources;110
7.6.2.1;6.2.1 Classical CCDs;110
7.6.2.2;6.2.2 Galactose-?-1,3-Galactose;110
7.6.3;6.3 Structural Considerations;110
7.6.3.1;6.3.1 Classical CCDs;110
7.6.3.2;6.3.2 Galactose-?-1,3-Galactose;111
7.6.4;6.4 Frequency of Sensitization and Allergenicity;111
7.6.4.1;6.4.1 Classical CCDs;111
7.6.4.2;6.4.2 Galactose-?-1,3-Galactose;112
7.6.5;6.5 Clinical Assessment of Allergenicity;113
7.6.5.1;6.5.1 Classical CCDs;113
7.6.5.2;6.5.2 Galactose-?-1,3-Galactose;114
7.6.6;6.6 Unresolved Issues;115
7.6.7;6.7 Relevance for Allergy Diagnostic Tests and Availability of Reagents for In Vitro or In Vivo Testing;115
7.6.7.1;6.7.1 Classical CCDs;115
7.6.7.2;6.7.2 Galactose-?-1,3-Galactose;118
7.6.8;6.8 Evaluating the Clinical Relevance of CCDs;118
7.6.8.1;6.8.1 Classical CCDs;118
7.6.8.2;6.8.2 Galactose-?-1,3-Galactose;120
7.6.9;6.9 Conclusion: Implications for Everyday Clinical Practice;121
7.6.10;References;121
8;Part II: Test Systems, Singleplex Analysis and Multiplex Analysis;125
8.1;7: Molecular Allergy Diagnostics Using IgE Singleplex Assays: Methodological and Practical Considerations;126
8.1.1;7.1 Introduction;126
8.1.1.1;7.1.1 Atopy and Allergen-Specific IgE;126
8.1.1.2;7.1.2 IgE, IgE Receptors, and the Effector Phase of Allergic Reactions: Background Information and Relevance in IgE Antibody Diagnostics;127
8.1.1.3;7.1.3 The IgE Repertoire: A Phenomenon with Complex Variables;129
8.1.1.4;7.1.4 Techniques to Detect Sensitization in Routine Diagnostics;130
8.1.2;7.2 Technological Basis of IgE Determination;131
8.1.2.1;7.2.1 Test Design and Test Components;131
8.1.2.2;7.2.2 Detection Thresholds in sIgE Determination;140
8.1.2.3;7.2.3 Specific IgE-Total IgE Ratio;141
8.1.2.4;7.2.4 Isoforms: Natural Variants of Allergen Molecules;141
8.1.3;7.3 Possible Applications for Allergen Molecules in IgE Diagnostics;142
8.1.3.1;7.3.1 Distinction Between Purified and Recombinantly Produced Components;144
8.1.3.2;7.3.2 Laboratory-Scale Evaluation: Assay Sensitivity and Analytical Specificity (Selectivity);148
8.1.3.3;7.3.3 Universal Arguments for the Use of Molecular Allergens in IgE Diagnostics;151
8.1.4;7.4 Clinical Evaluation: Diagnostic Sensitivity and Specificity;152
8.1.5;7.5 Interpretation to Establish Clinical Relevance;164
8.1.6;7.6 Potential and Quantitative Concepts of Molecular Allergology;165
8.1.6.1;7.6.1 The Use of Singleplex IgE Assays in Bet v 1-Related Cross-Reactivity;166
8.1.6.2;7.6.2 The Use of Singleplex IgE Assays in Profilin Sensitization;166
8.1.6.3;7.6.3 The Use of Singleplex IgE Assays Against Storage Proteins;167
8.1.7;References;169
8.2;8: Spiking with Recombinant Individual Allergens for Improvement of Allergen Extracts;172
8.2.1;8.1 Introduction;172
8.2.2;8.2 Improvement of Diagnostics Through Allergen Addition in Latex Allergy;174
8.2.3;8.3 Benefits and Disadvantages of Allergen Addition in Hazelnut Allergy;176
8.2.4;8.4 Improvement of Test Sensitivity by Allergen Addition in Yellow Jacket Venom Allergy;177
8.2.5;8.5 Additional Value of Molecular Diagnostics and Conclusion for Routine Clinical Practice;180
8.2.6;8.6 Conclusion for Clinical Routine;181
8.2.7;Bibliography;181
8.3;9: Molecular Allergy Diagnostics Using Multiplex Assays;183
8.3.1;9.1 Introduction;184
8.3.2;9.2 Molecular Allergy Diagnostics Using Multiplex Assays;185
8.3.3;9.3 Immuno Solid-Phase Allergen Chip (ISAC);190
8.3.3.1;9.3.1 Test Procedure;190
8.3.3.2;9.3.2 Test Performance;192
8.3.3.2.1;9.3.2.1 Intra- and Inter-Assay Variance;192
8.3.3.2.2;9.3.2.2 Linearity and Limit of Detection (LoD);193
8.3.3.2.3;9.3.2.3 Sample Material and Interference;195
8.3.3.3;9.3.3 Comparison of sIgE to Single Allergens Determined in Multiplex (ISAC sIgE 112) and Singleplex Assays (ImmunoCAP);195
8.3.4;9.4 Molecular Allergy Diagnostics Using Multiplex Assays in Clinical Routine;197
8.3.4.1;9.4.1 Allergen Spectrum Available and Potential Advantages in Diagnostics;197
8.3.4.2;9.4.2 Added Benefits Conferred by Molecular Allergy Diagnostics in Clinical Routine;200
8.3.4.2.1;9.4.2.1 Differentiation Between Genuine Sensitization and Cross-­Reactivity with Inhalant Allergens;200
8.3.4.2.2;9.4.2.2 Identification of Sensitizations to Food Allergens Associated with a High Risk for Severe Allergic Reactions;202
8.3.4.3;9.4.3 Paralysis Through Analysis? Interpretation Supported by Intelligent Software and Results Evaluated by the Physician;204
8.3.4.4;9.4.4 Special Features in Routine Use;207
8.3.5;9.5 Molecular Allergy Diagnostics Using Multiplex Assays in Research;208
8.3.5.1;9.5.1 New Insights Gained Using ISAC Technology;208
8.3.5.1.1;9.5.1.1 Diversity of Sensitization Profiles;209
8.3.5.1.2;9.5.1.2 Developing Sensitization Profiles;209
8.3.5.1.3;9.5.1.3 Prescribing Behavior in Allergen-Specific Immunotherapy (SIT);210
8.3.5.2;9.5.2 The Use of Individually Tailored Allergen Chips in Research;210
8.3.6;9.6 Summary and Perspectives;211
8.3.7;References;213
9;Part III: Marker Allergens;215
9.1;10: Marker Allergens and Panallergens in Tree and Grass Pollen Allergy;216
9.1.1;10.1 Introduction;217
9.1.2;10.2 Allergen Sources in Trees and Grasses;217
9.1.2.1;10.2.1 Grasses;217
9.1.2.2;10.2.2 Trees;219
9.1.3;10.3 Important Grass Pollen Allergens;220
9.1.3.1;10.3.1 Allergens Found in all Poaceae Grasses;220
9.1.3.1.1;10.3.1.1 Marker Allergen for all Poaceae Grasses: Group 1 (Phl p 1);220
9.1.3.1.2;10.3.1.2 Group 13;222
9.1.3.2;10.3.2 Allergens Found Only in Pooideae Grasses;222
9.1.3.2.1;10.3.2.1 Marker Allergen for Pooideae: Group 5 (Phl p 5);222
9.1.3.2.2;10.3.2.2 Other Pooideae-Specific Allergens;223
9.1.3.3;10.3.3 Allergens from Tropical and Subtropical Grasses;223
9.1.3.4;10.3.4 Marker Allergens for Grass Pollen Allergy: Summary;224
9.1.3.5;10.3.5 Carbohydrate Sensitivity in Grass Pollen Allergic Patients;224
9.1.4;10.4 Important Tree Pollen Allergens;225
9.1.4.1;10.4.1 Allergens of Trees of the Order Fagales;225
9.1.4.1.1;10.4.1.1 Marker Allergen for Fagales: Bet v 1;225
9.1.4.1.2;10.4.1.2 Other Fagales-Specific Minor Allergens;227
9.1.4.2;10.4.2 Allergens of Trees of the Order Lamiales;227
9.1.4.2.1;10.4.2.1 Marker Allergen for Lamiales: Ole e 1;227
9.1.4.2.2;10.4.2.2 Other Lamiales-Specific Allergens;228
9.1.4.3;10.4.3 Allergens of Trees of the Order Proteales;228
9.1.4.4;10.4.4 Allergens of Trees of the Order Cupressales;229
9.1.5;10.5 Panallergens: Markers for Cross-Reactivity;229
9.1.5.1;10.5.1 Polcalcins;230
9.1.5.2;10.5.2 Profilins;230
9.1.5.3;10.5.3 Panallergens: Summary;230
9.1.6;10.6 Conclusions for Clinical Routine Work;231
9.1.7;References;233
9.2;11: Marker Allergens of Weed Pollen: Basic Considerations and Diagnostic Benefits in Routine Clinical Practice;240
9.2.1;11.1 Introduction;240
9.2.2;11.2 Allergen Nomenclature;242
9.2.3;11.3 Structure and Biological Function of Relevant Protein Families;242
9.2.3.1;11.3.1 Pectate Lyases;242
9.2.3.2;11.3.2 Defensin-Like Proteins;243
9.2.3.3;11.3.3 Nonspecific Lipid Transfer Proteins;244
9.2.3.4;11.3.4 Ole e 1-Like Proteins;244
9.2.4;11.4 Clinical Relevance of Allergens;244
9.2.4.1;11.4.1 Pectate Lyases;244
9.2.4.2;11.4.2 Defensin-Like Proteins;245
9.2.4.3;11.4.3 Nonspecific Lipid Transfer Proteins (nsLTP);245
9.2.4.4;11.4.4 Ole e 1-Like Proteins;245
9.2.5;11.5 Sensitization Frequencies;245
9.2.6;11.6 Cross-Reactive Versus Marker Allergens;246
9.2.7;11.7 Allergy Diagnosis;248
9.2.8;11.8 Added Value of Molecular Allergy Diagnostics;248
9.2.9;11.9 Therapeutic Recommendations;250
9.2.10;11.10 Perspectives;250
9.2.11;11.11 Conclusions for Routine Clinical Practice;251
9.2.12;References;251
9.3;12: Molecular Diagnostics for Peanut Allergy;254
9.3.1;12.1 The Peanut s Role as an Allergen;254
9.3.2;12.2 Individual Peanut Allergens;255
9.3.2.1;12.2.1 Primary Major Allergens: Storage Proteins;257
9.3.2.2;12.2.2 Primary Minor Allergens: Oleosins;257
9.3.2.3;12.2.3 Secondary Allergens: nsLTPs and Cross-Reactive Aeroallergens;258
9.3.3;12.3 Clinical Data Concerning Molecular Diagnostics;258
9.3.4;12.4 Diagnostics with Peanut Allergens;262
9.3.4.1;12.4.1 Available Single Allergens;262
9.3.4.2;12.4.2 Potential Benefits of Molecular Diagnostics with Peanut Allergens;262
9.3.4.3;12.4.3 Procedure for Diagnosing Peanut Allergy in Childhood (<14 Years);263
9.3.4.4;12.4.4 Common Peanut Cross-Reactions Regarding Birch Pollen Sensitization;265
9.3.4.5;12.4.5 Less Common Sensitization Patterns in Peanut Allergy;266
9.3.5;12.5 Cross-Reactive Allergens;266
9.3.6;12.6 Conclusions: Relevance in Daily Clinical Practice;266
9.3.7;References;267
9.4;13: Molecular Diagnostics for Tree Nut Allergy;270
9.4.1;13.1 Allergen Determination;270
9.4.2;13.2 Structure, Function, and Role of Allergens;272
9.4.3;13.3 Sensitization Frequencies;273
9.4.4;13.4 Serological Cross-Reactions;273
9.4.5;13.5 Diagnostics: Available Single Allergens;274
9.4.5.1;13.5.1 Hazelnut;274
9.4.5.2;13.5.2 Walnut;276
9.4.5.3;13.5.3 Other Nuts;278
9.4.6;13.6 Clinical Value of Molecular Diagnostics;278
9.4.7;13.7 Perspectives;279
9.4.8;13.8 Conclusions: Relevance in Daily Clinical Practice;279
9.4.9;References;281
9.5;14: Molecular Diagnostics of Allergy to Fruits and Vegetables;283
9.5.1;14.1 Introduction;283
9.5.2;14.2 Epidemiology of Fruit and Vegetable Allergy;284
9.5.3;14.3 Potential Benefits of Molecular Diagnostics in  Food Allergy;284
9.5.4;14.4 Allergies to Fruits and Vegetables: The Most Important Allergen Families;285
9.5.5;14.5 Molecular Diagnostics in Vegetable Allergy;286
9.5.5.1;14.5.1 Celery Root Allergy;286
9.5.5.2;14.5.2 Carrot Allergy;287
9.5.5.3;14.5.3 Tomato Allergy;288
9.5.6;14.6 Molecular Diagnostics in Fruit Allergy;289
9.5.6.1;14.6.1 Kiwi Fruit Allergy;290
9.5.6.2;14.6.2 Peach Allergy;294
9.5.6.3;14.6.3 Latex-Fruit Syndrome and the Relevance of the Hevein-­Like Domain;295
9.5.7;14.7 Summary and Outlook;295
9.5.8;14.8 Conclusion: Potential for Routine Clinical Practice;296
9.5.9;References;296
9.6;15: Cow s Milk and Hen s Egg Allergy: What Do Molecular-Based Allergy Diagnostics Have to Offer?;302
9.6.1;15.1 Introduction;302
9.6.2;15.2 Allergen Nomenclature;303
9.6.3;15.3 Properties of the Most Relevant Allergens;304
9.6.3.1;15.3.1 Cow s Milk;304
9.6.3.2;15.3.2 Hen s Egg;306
9.6.3.3;15.3.3 Special Case: Cow s Milk and Hen s Egg in Baked Foods;307
9.6.4;15.4 Prevalence, Distribution, and Prognosis of Sensitization;307
9.6.4.1;15.4.1 Prognosis;308
9.6.5;15.5 Diagnostic Methods;309
9.6.5.1;15.5.1 Assessing Clinical Relevance;309
9.6.5.2;15.5.2 Assessing Tolerance in Baked Goods;310
9.6.6;15.6 Additional Benefits Conferred by Molecular-Based Allergy Diagnostics;311
9.6.7;15.7 Treatment and Recommendations;311
9.6.8;15.8 Conclusions for Clinical Practice;312
9.6.9;References;312
9.7;16: Molecular and Extract-Based Diagnostics in Meat Allergy;315
9.7.1;16.1 Introduction to Molecular and Extract-Based Diagnostics in Meat Allergy;315
9.7.2;16.2 Pork-Cat Syndrome, a Link Between Pet Dander and Meat;316
9.7.2.1;16.2.1 Allergen Structure and Function;316
9.7.2.2;16.2.2 Allergen Prevalence and Sensitization;317
9.7.2.3;16.2.3 Diagnosis and Recommendations;318
9.7.3;16.3 Type I Hypersensitivity Reactions to Galactose-?-1,3-Galactose in Red Meat Allergy;319
9.7.3.1;16.3.1 Carbohydrate Side Chain Galactose-?-1,3-Galactose (?-Gal);319
9.7.3.2;16.3.2 Type I Allergy to ?-Gal and the Role of Tick Bites;322
9.7.3.3;16.3.3 Diagnostic Measures in Delayed Type I Hypersensitivity Reactions to Red Meat and Innards;324
9.7.3.4;16.3.4 Clinical Relevance and Particular Features of Delayed Type I Hypersensitivity Reactions to Red Meat and Innards;324
9.7.4;16.4 Bird-Egg Syndrome and Genuine Poultry Meat Allergy;326
9.7.4.1;16.4.1 Types of Poultry Meat Allergy;326
9.7.4.2;16.4.2 Allergen Structure and Function;326
9.7.4.3;16.4.3 Allergen Prevalence and Sensitization in Bird-Egg Syndrome-Related Poultry Meat Allergy;327
9.7.4.4;16.4.4 Allergen Prevalence and Sensitization in Primary Poultry Meat Allergy;328
9.7.4.5;16.4.5 Immunologic Relationships Between Poultry Meat, Red Meat, and Other Foods;329
9.7.4.6;16.4.6 Diagnosis and Recommendations;330
9.7.5;16.5 Advantage of Molecular Diagnostics;331
9.7.6;16.6 Recommendations for Clinical Practice;331
9.7.7;References;332
9.8;17: Molecular Diagnostics in Food-­Dependent Exercise-Induced Anaphylaxis;337
9.8.1;17.1 Introduction;337
9.8.2;17.2 Allergen Identification;339
9.8.3;17.3 Structure, Function, and Importance of the Allergens;341
9.8.4;17.4 Sensitization Prevalences/Distribution;342
9.8.5;17.5 Cross-Reactive Versus Marker Allergens;343
9.8.6;17.6 Diagnostic Workup;344
9.8.7;17.7 Added Benefits Conferred by Molecular Allergy Diagnostics;346
9.8.8;17.8 Therapy and Recommendations;347
9.8.9;17.9 Perspectives;347
9.8.10;References;348
9.9;18: Benefits and Limitations of Recombinant Allergens in Diagnostics of Insect Venom Allergy;351
9.9.1;18.1 Introduction;351
9.9.2;18.2 Structure, Function, and Relevance of Hymenoptera Venom Allergens;354
9.9.3;18.3 Methodological Aspects for the Production of Recombinant Hymenoptera Venom Allergens;359
9.9.3.1;18.3.1 Recombinant Allergens from Eukaryotic Cells;359
9.9.4;18.4 Benefits of Molecular Diagnostics;360
9.9.4.1;18.4.1 Molecular Diagnostics for Differentiation of Double Sensitizations;360
9.9.4.2;18.4.2 Use of Recombinant Insect Venom Allergens in Clinical Routine Diagnostics;362
9.9.4.3;18.4.3 Improvement of Test Sensitivity by Recombinant Allergens;364
9.9.4.4;18.4.4 Potential Relevance for Specific Immunotherapy;366
9.9.5;18.5 Open Questions and Future Perspectives;367
9.9.6;18.6 Conclusion for Daily Practice;368
9.9.7;References;369
9.10;19: Molecular Diagnostics in Allergy to Mammals;373
9.10.1;19.1 Introduction;373
9.10.2;19.2 Protein Structure and Function;374
9.10.3;19.3 Current Status of Identified Allergenic Molecules from Different Mammalian Allergen Sources;375
9.10.3.1;19.3.1 Cat Allergenic Molecules;375
9.10.3.2;19.3.2 Dog Allergenic Molecules;376
9.10.3.3;19.3.3 Horse Allergenic Molecules;377
9.10.3.4;19.3.4 Cattle Allergenic Molecules;377
9.10.3.5;19.3.5 Rabbit Allergenic Molecules;378
9.10.3.6;19.3.6 Mouse and Rat Allergenic Molecules;378
9.10.3.7;19.3.7 Guinea Pig Allergenic Molecules;379
9.10.3.8;19.3.8 Hamster Allergenic Molecules;379
9.10.4;19.4 Prevalence of Sensitization/Distribution;379
9.10.5;19.5 Cross-Reactive Versus Marker Allergens in Mammals;380
9.10.6;19.6 Problems in Diagnosing Sensitization to Animals;381
9.10.7;19.7 Current Additional Benefits from Molecular Diagnostics;383
9.10.8;19.8 Therapy and Recommendations;383
9.10.9;19.9 Outlook;384
9.10.10;19.10 Conclusion: Potential for Routine Clinical Practice;384
9.10.11;References;386
9.11;20: Extract-Based and Molecular Diagnostics in Fish Allergy;390
9.11.1;20.1 Introduction;390
9.11.2;20.2 Allergens: Nomenclature;391
9.11.3;20.3 Allergens: Structure;391
9.11.4;20.4 Allergens: Function;394
9.11.5;20.5 Allergens: Relevance;395
9.11.6;20.6 Sensitization Prevalence;396
9.11.7;20.7 Cross-Reactive Versus Marker Allergens;397
9.11.8;20.8 Diagnostics;398
9.11.9;20.9 Additional Benefit from Molecular Diagnostics;399
9.11.10;20.10 Therapy and Recommendation;402
9.11.11;20.11 Outlook;402
9.11.12;20.12 Conclusions: Potential for Everyday Clinical Practice;403
9.11.13;References;403
9.12;21: Allergens and Molecular Diagnostics of Shellfish Allergy;407
9.12.1;21.1 Background;407
9.12.2;21.2 Classification of Shellfish Groups;408
9.12.3;21.3 Prevalence of Shellfish Allergy;409
9.12.4;21.4 Structure and Biological Functions of Shellfish Allergens;411
9.12.5;21.5 Clinical and Immunological Cross-Reactivity;415
9.12.5.1;21.5.1 Potential Advantages of Component-Resolved Diagnosis (CRD) in Shellfish Allergy;416
9.12.6;21.6 Diagnostics Separating IgE-Mediated Allergy from Other Reactions;417
9.12.7;21.7 Outlook for Future Diagnostic Options;418
9.12.8;21.8 Suggestions for Present Clinical Practice;418
9.12.9;References;420
9.13;22: Allergens, Diagnostics, and Therapeutic Aspects in House Dust Mite Allergy;423
9.13.1;22.1 Introduction;423
9.13.2;22.2 Designation of Allergens;424
9.13.3;22.3 Structure and Function of Allergens;424
9.13.4;22.4 Importance of the Allergens;428
9.13.5;22.5 Frequency of Sensitization/Distribution;429
9.13.6;22.6 Cross-Reactive Allergens/Marker Allergens;429
9.13.7;22.7 Diagnosis;430
9.13.8;22.8 Added Value of Molecular Diagnosis;431
9.13.9;22.9 Therapy and Recommendations;431
9.13.10;22.10 Perspectives;433
9.13.11; Conclusion;433
9.13.12;References;434
9.14;23: Cockroach, Tick, Storage Mite, and Other Arthropod Allergies: Molecular Aspects;437
9.14.1;23.1 Introduction;437
9.14.2;23.2 Cockroach Allergy;438
9.14.2.1;23.2.1 Exposure and Distribution;438
9.14.2.2;23.2.2 Allergen Identification;439
9.14.2.3;23.2.3 Function and Structure;440
9.14.2.4;23.2.4 Relevance and Sensitization Frequency;441
9.14.2.5;23.2.5 Cross-Reactive Allergens;441
9.14.3;23.3 Storage Mite Allergy;442
9.14.3.1;23.3.1 Exposure and Distribution;442
9.14.3.2;23.3.2 Allergen Identification;442
9.14.3.3;23.3.3 Relevance;442
9.14.3.4;23.3.4 Cross-Reactive Allergens;442
9.14.4;23.4 Tick Allergy;443
9.14.4.1;23.4.1 Exposure and Distribution;443
9.14.4.2;23.4.2 Allergen Identification;444
9.14.5;23.5 Allergies to Other Arthropods;444
9.14.6;23.6 Diagnostics and the Added Benefit of Molecular-Based Diagnosis;448
9.14.7;23.7 Treatment and Diagnostic Outlook;449
9.14.8;References;449
9.15;24: Mold Allergens and Their Importance in Molecular Allergy Diagnosis;453
9.15.1;24.1 Background;453
9.15.2;24.2 Classification of Fungal Allergens;454
9.15.3;24.3 Mold Exposure and Health Risks;454
9.15.4;24.4 Mold Allergens Belong to Various Protein Families, Most Often with Enzymatic Function in the Organism;458
9.15.4.1;24.4.1 Proteases;459
9.15.4.2;24.4.2 Ribosomal Proteins;459
9.15.4.3;24.4.3 Enolases;459
9.15.4.4;24.4.4 Dehydrogenases;459
9.15.4.5;24.4.5 Thioredoxins;460
9.15.4.6;24.4.6 Heat Shock Proteins;460
9.15.4.7;24.4.7 Peroxisomal Membrane Proteins;460
9.15.4.8;24.4.8 MnSODs;460
9.15.4.9;24.4.9 Flavodoxins;460
9.15.4.10;24.4.10 Cyclophilins;461
9.15.5;24.5 Commercially Available Single Allergens Originating from Mold;461
9.15.5.1;24.5.1 Specific IgG Tests;463
9.15.6;24.6 Outlook;463
9.15.7;24.7 Conclusions for Routine Clinical Practice;464
9.15.8;References;464
9.16;25: Latex Allergens: Source of Sensitization and Single Allergens;467
9.16.1;25.1 Introduction;467
9.16.2;25.2 Source of Proteins and Denomination of Allergens;468
9.16.3;25.3 Function of NRL Allergens;468
9.16.4;25.4 Importance of the Major Allergens;470
9.16.5;25.5 Dissemination of Latex Allergy;471
9.16.6;25.6 Cross-Reactive Carbohydrate Determinants (CCDs);472
9.16.7;25.7 Latex-Food Syndrome;472
9.16.8;25.8 Diagnosis with Single Latex Allergens;474
9.16.9;25.9 Perspectives (Conclusions);474
9.16.10;References;476
10;Part IV: Designer Allergens, Hypoallergens and Fusion Allergens;479
10.1;26: Recombinant Allergens in Specific Immunotherapy;480
10.1.1;26.1 Introduction;480
10.1.2;26.2 Advantages and Opportunities Posed by Recombinant Allergens for Allergen-Specific Immunotherapy;481
10.1.2.1;26.2.1 Recombinant Allergens for Specific Immunotherapy: Why?;481
10.1.2.2;26.2.2 The Challenge: Selecting the Relevant Allergens;482
10.1.2.3;26.2.3 Various Treatment Strategies Using Recombinant Allergens;484
10.1.3;26.3 Clinical Experience with Recombinant Allergens;485
10.1.3.1;26.3.1 Regulatory Requirements;485
10.1.3.2;26.3.2 Studies with Unmodified Recombinant Allergens;486
10.1.3.3;26.3.3 Studies with Hypoallergenic Recombinant Allergenoids;488
10.1.3.4;26.3.4 Studies Involving Alternative Concepts;490
10.1.4;26.4 Molecular Diagnosis for Molecular Treatment?;491
10.1.5;References;492
10.2;27: Definition and Design of Hypoallergenic Foods;494
10.2.1;27.1 Introduction;495
10.2.2;27.2 Definition of Hypoallergenic Foods;496
10.2.3;27.3 Design and Evaluation of Hypoallergenic Foods;497
10.2.4;27.4 Methods of Gene Silencing to Produce Hypoallergenic Foods;498
10.2.5;27.5 Allergen Reduction Achieved in Allergen Source Models of Plant-Based Foods;500
10.2.5.1;27.5.1 Rice (Oryza sativa);500
10.2.5.2;27.5.2 Soybean (Glycine max);502
10.2.5.3;27.5.3 Apple (Malus domestica);503
10.2.5.4;27.5.4 Tomato (Solanum lycopersicum, Formerly: Lycopersicon esculentum);504
10.2.5.5;27.5.5 Carrot (Daucus carota);507
10.2.5.6;27.5.6 Peanut (Arachis hypogaea);508
10.2.6;27.6 Acceptance of Hypoallergenic GM Foods Among Consumers;509
10.2.7;27.7 Additional Benefits of Molecular Diagnostics;510
10.2.8;27.8 Treatment and Recommendations;510
10.2.9;27.9 Perspectives;511
10.2.10; Conclusions;512
10.2.11;References;513
11;Index;519mehr

Autor

Thilo Jakob is Professor for Dermatology and Allergology at the Medical Faculty, Justus-Liebig-University in Gießen, and Chair of the Department of Dermatology and Allergology at the University Medical Center Giessen and Marburg (UKGM), Campus Giessen, Germany. He trained with Prof. Ivan Roitt, University College, London, Dres Steven Katz and Mark Udey, N.I.H. Bethesda, USA, and Prof. Johannes Ring, Technische Universität Munich, Germany. His research interests are focused on clinical and experimental allergology and immunodermatology, related to which he has published 110 original articles, with a cumulative impact factor of 672, over 3000 citations, 97 reviews and book chapters. He was awarded numerous research and teaching prizes such as the University Teaching Award in 2010 and the e-learing Award by the Albert Ludwigs University Freiburg in 2013. He is currently board member of the Executive Committee of the German Society of Allergy and Clinical Immunology (DGAKI), past member of the Executive Committee European Academy of Allergy and Clinical Immunology (2005-2009) and past Chairman of the Immunology Section of the EAACI. He is currently the Editor in Chief of the Allergo Journal International, the official journal of the German Society of Allergy and Clinical Immunology and the Medical Association of German Allergist (since 2010), Associate Editor of International Archives of Allergy and Immunology and serves on the editorial board of a number of allergy and dermatology journals.

Jörg Kleine-Tebbe is working as an allergist and dermatologist at the Allergy and Asthma Center Westend, Berlin, a private practice and research center. After the MD in medicine, he earned a Clinical and Research Fellowship at the Asthma OPD and Department of Clinical Immunology (Chair: Prof. Dr. Gert Kunkel), University Hospital Rudolf Virchow, Freie Universität Berlin, Germany. He continued with allergy & immunology related basic research (Visiting Instructor in Medicine) at the Johns Hopkins Asthma & Allergy Center, Allergy and Clinical Immunology Division (L. M. Lichtenstein, D. G. Marsh), Baltimore MD, USA. Afterwards he became Senior Resident and Instructor at the University Dermatology Hospital in Leipzig. Later he transferred his habilitation and lectureship to the Charité, Berlin (University Hospital of Dermatology and Allergology, Humboldt University) and, successively, joined the team of Prof. Dr. Gert Kunkel, at Allergy and Asthma Center Westend (AAZW), a Multi-Group Private Practice for Allergology, Internal Medicine and Dermatology with an integrated Clinical Research Center (UZDAA) for Allergology, Airway & Lung Diseases and Dermatology. Jörg Kleine-Tebbe has authored and co-authored numerous national and international guidelines and has been Chairman of the EAACI Interest Group Allergy Diagnosis, is currently Board Member of the EAACI Interest Group Immunotherapy, member of the AAAAI Immunotherapy, Allergen Standardization and Allergy Diagnostics Committee and the AAAAI Practice, Diagnostics and Therapeutics Committee and Executive Committee member of the German Society of Allergy and clinical Immunology (DGAKI).