Molecular Allergy Diagnostics (eBook)

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).   

Foreword 1 5
Foreword 2 7
Preface 9
Molecular Allergology: From Research Topic to Innovative Allergy Diagnosis 9
Acknowledgments 11
Contributors 16
Contents 13
Part I: Protein Families and Relationships 20
1: Introduction to Molecular Allergology: Protein Families, Databases, and Potential Benefits 21
1.1 The Era of Molecular Allergology 22
1.2 Immediate-Type Allergens and Their Names 23
1.3 Sequence and Structure: From T Cell to Antibody (B Cell) Epitopes 24
1.4 Protein Families and Relatedness of Type I Allergens 24
1.5 Databases for Clinical Practice and Research 27
1.6 Potential Use of Single Allergens 30
1.6.1 Quantification of Allergens in Extracts 30
1.6.2 Molecular Epidemiology 31
1.6.3 Diagnostics with Single Allergens 31
1.7 Scope and Limits of Interpretation 33
1.8 Immunotherapy and Single Allergens 33
1.9 Molecular Allergology Drives Innovation 34
Conclusions 35
References 35
2: Bet v 1 and its Homologs: Triggers of Tree-Pollen Allergy and Birch Pollen-­Associated Cross-Reactions 38
2.1 Introduction 38
2.2 Biological Facts and Characteristics 39
2.2.1 Allergen Identification 39
2.2.2 Family 39
2.2.3 Bet v 1 and the Bet v 1 Superfamily 39
2.2.4 Physiological Function of Bet v 1 40
2.2.5 Characteristics 41
2.3 Importance of Bet v 1 and Related Allergens 41
2.3.1 Sources of Bet v 1 and its Biological and Allergological Role 41
2.3.2 Prevalence and Distribution of Sensitization 42
2.3.3 Bet v 1: A Marker Allergen for Tree (Fagales Order) Pollen Sensitization and IgE Cross-Reactivity to Plant-Derived Foods 42
2.3.3.1 Bet v 1 Cross-Reactive Inhalant Allergens 42
2.3.3.2 Bet v 1 Cross-Reactive Food Allergens 43
2.4 Diagnosis 45
2.4.1 Airway Symptoms Caused by Tree Pollen Allergy 45
2.4.2 Bet v 1-Associated Cross-Allergies to Plant-Derived Foods 47
2.4.3 Added Benefits of Molecular Diagnostics 54
2.4.3.1 Advantages of Bet v 1 in Molecular Diagnostics 55
2.4.3.2 Possibilities of Diagnostics Using Bet v 1-Homologous Allergens 55
2.5 Therapy and Recommendations 57
2.6 Perspectives 57
2.7 Conclusions for Clinical Practice 57
References 57
3: The Concept of Pollen Panallergens: Profilins and Polcalcins 60
3.1 Introduction 60
3.2 Allergen Nomenclature 61
3.3 Structure and Function of Profilins 61
3.4 Relevance of Profilins 63
3.5 Sensitization to Profilins 64
3.6 Structure and Function of Polcalcins 65
3.7 Relevance of Polcalcins 65
3.8 Diagnosis of Relevant Multi-Sensitizations to Pollen 66
3.9 Component-Resolved Diagnosis of Panallergen Sensitizations 68
3.10 Clinical Relevance of Panallergens 68
3.11 Extract Selection for Allergen Immunotherapy (AIT) 70
3.12 Conclusions from a Clinical Perspective 71
References 71
4: Stable Plant Food Allergens I: Lipid-Transfer Proteins 74
4.1 Introduction 74
4.2 Structure of Allergens 75
4.3 Biological Function of Allergens 77
4.4 Frequency of Sensitization and Geographic Distribution 77
4.5 Clinical Relevance 80
4.6 IgE Cross-Reactivity Between LTPs 81
4.7 Diagnosis by Sensitization Tests with LTPs and LTP-­Containing Extracts 84
4.8 Clinical Relevance of LTP Sensitization 85
4.9 Therapeutic Recommendations 87
4.10 Other Perspectives 87
4.11 Implications for Routine Clinical Practice 87
References 88
5: Stable Plant Food Allergens II: Storage Proteins 93
5.1 Introduction 93
5.2 Allergen Nomenclature 94
5.3 Protein Structures 94
5.4 Functions 97
5.5 Relevance 98
5.6 Complex Cross-Reactivity Among Storage Proteins 98
5.7 Diagnostic Challenges 101
5.8 Additional Possible Benefits from Molecular Diagnostics 102
5.9 Outlook 104
5.10 Conclusion: Potential for Routine Clinical Practice 104
References 104
6: Cross-Reactive Carbohydrate Determinants: Diagnostic and Clinical Relevance 107
6.1 Introduction 108
6.1.1 Cross-Reactive Carbohydrate Determinants 109
6.2 Allergen Sources 110
6.2.1 “Classical” CCDs 110
6.2.2 Galactose-?-1,3-Galactose 110
6.3 Structural Considerations 110
6.3.1 “Classical” CCDs 110
6.3.2 Galactose-?-1,3-Galactose 111
6.4 Frequency of Sensitization and Allergenicity 111
6.4.1 “Classical” CCDs 111
6.4.2 Galactose-?-1,3-Galactose 112
6.5 Clinical Assessment of Allergenicity 113
6.5.1 “Classical” CCDs 113
6.5.2 Galactose-?-1,3-Galactose 114
6.6 Unresolved Issues 115
6.7 Relevance for Allergy Diagnostic Tests and Availability of Reagents for In Vitro or In Vivo Testing 115
6.7.1 “Classical” CCDs 115
6.7.2 Galactose-?-1,3-Galactose 118
6.8 Evaluating the Clinical Relevance of CCDs 118
6.8.1 “Classical” CCDs 118
6.8.2 Galactose-?-1,3-Galactose 120
6.9 Conclusion: Implications for Everyday Clinical Practice 121
References 121
Part II: Test Systems, Singleplex Analysis and Multiplex Analysis 125
7: Molecular Allergy Diagnostics Using IgE Singleplex Assays: Methodological and Practical Considerations 126
7.1 Introduction 126
7.1.1 Atopy and Allergen-Specific IgE 126
7.1.2 IgE, IgE Receptors, and the Effector Phase of Allergic Reactions: Background Information and Relevance in IgE Antibody Diagnostics 127
7.1.3 The IgE Repertoire: A Phenomenon with Complex Variables 129
7.1.4 Techniques to Detect Sensitization in Routine Diagnostics 130
7.2 Technological Basis of IgE Determination 131
7.2.1 Test Design and Test Components 131
7.2.2 Detection Thresholds in sIgE Determination 140
7.2.3 Specific IgE–Total IgE Ratio 141
7.2.4 Isoforms: Natural Variants of Allergen Molecules 141
7.3 Possible Applications for Allergen Molecules in IgE Diagnostics 142
7.3.1 Distinction Between Purified and Recombinantly Produced Components 144
7.3.2 Laboratory-Scale Evaluation: Assay Sensitivity and Analytical Specificity (Selectivity) 148
7.3.3 Universal Arguments for the Use of Molecular Allergens in IgE Diagnostics 151
7.4 Clinical Evaluation: Diagnostic Sensitivity and Specificity 152
7.5 Interpretation to Establish Clinical Relevance 164
7.6 Potential and Quantitative Concepts of Molecular Allergology 165
7.6.1 The Use of Singleplex IgE Assays in Bet v 1-Related Cross-Reactivity 166
7.6.2 The Use of Singleplex IgE Assays in Profilin Sensitization 166
7.6.3 The Use of Singleplex IgE Assays Against Storage Proteins 167
References 169
8: Spiking with Recombinant Individual Allergens for Improvement of Allergen Extracts 172
8.1 Introduction 172
8.2 Improvement of Diagnostics Through Allergen Addition in Latex Allergy 174
8.3 Benefits and Disadvantages of Allergen Addition in Hazelnut Allergy 176
8.4 Improvement of Test Sensitivity by Allergen Addition in Yellow Jacket Venom Allergy 177
8.5 Additional Value of Molecular Diagnostics and Conclusion for Routine Clinical Practice 180
8.6 Conclusion for Clinical Routine 181
Bibliography 181
9: Molecular Allergy Diagnostics Using Multiplex Assays 183
9.1 Introduction 184
9.2 Molecular Allergy Diagnostics Using Multiplex Assays 185
9.3 Immuno Solid-Phase Allergen Chip (ISAC) 190
9.3.1 Test Procedure 190
9.3.2 Test Performance 192
9.3.2.1 Intra- and Inter-Assay Variance 192
9.3.2.2 Linearity and Limit of Detection (LoD) 193
9.3.2.3 Sample Material and Interference 195
9.3.3 Comparison of sIgE to Single Allergens Determined in Multiplex (ISAC sIgE 112) and Singleplex Assays (ImmunoCAP) 195
9.4 Molecular Allergy Diagnostics Using Multiplex Assays in Clinical Routine 197
9.4.1 Allergen Spectrum Available and Potential Advantages in Diagnostics 197
9.4.2 Added Benefits Conferred by Molecular Allergy Diagnostics in Clinical Routine 200
9.4.2.1 Differentiation Between Genuine Sensitization and Cross-­Reactivity with Inhalant Allergens 200
9.4.2.2 Identification of Sensitizations to Food Allergens Associated with a High Risk for Severe Allergic Reactions 202
9.4.3 Paralysis Through Analysis? Interpretation Supported by Intelligent Software and Results Evaluated by the Physician 204
9.4.4 Special Features in Routine Use 207
9.5 Molecular Allergy Diagnostics Using Multiplex Assays in Research 208
9.5.1 New Insights Gained Using ISAC Technology 208
9.5.1.1 Diversity of Sensitization Profiles 209
9.5.1.2 Developing Sensitization Profiles 209
9.5.1.3 Prescribing Behavior in Allergen-Specific Immunotherapy (SIT) 210
9.5.2 The Use of Individually Tailored Allergen Chips in Research 210
9.6 Summary and Perspectives 211
References 213
Part III: Marker Allergens 215
10: Marker Allergens and Panallergens in Tree and Grass Pollen Allergy 216
10.1 Introduction 217
10.2 Allergen Sources in Trees and Grasses 217
10.2.1 Grasses 217
10.2.2 Trees 219
10.3 Important Grass Pollen Allergens 220
10.3.1 Allergens Found in all Poaceae Grasses 220
10.3.1.1 Marker Allergen for all Poaceae Grasses: Group 1 (Phl p 1) 220
10.3.1.2 Group 13 222
10.3.2 Allergens Found Only in Pooideae Grasses 222
10.3.2.1 Marker Allergen for Pooideae: Group 5 (Phl p 5) 222
10.3.2.2 Other Pooideae-Specific Allergens 223
10.3.3 Allergens from Tropical and Subtropical Grasses 223
10.3.4 Marker Allergens for Grass Pollen Allergy: Summary 224
10.3.5 Carbohydrate Sensitivity in Grass Pollen Allergic Patients 224
10.4 Important Tree Pollen Allergens 225
10.4.1 Allergens of Trees of the Order Fagales 225
10.4.1.1 Marker Allergen for Fagales: Bet v 1 225
10.4.1.2 Other Fagales-Specific Minor Allergens 227
10.4.2 Allergens of Trees of the Order Lamiales 227
10.4.2.1 Marker Allergen for Lamiales: Ole e 1 227
10.4.2.2 Other Lamiales-Specific Allergens 228
10.4.3 Allergens of Trees of the Order Proteales 228
10.4.4 Allergens of Trees of the Order Cupressales 229
10.5 Panallergens: Markers for Cross-Reactivity 229
10.5.1 Polcalcins 230
10.5.2 Profilins 230
10.5.3 Panallergens: Summary 230
10.6 Conclusions for Clinical Routine Work 231
References 233
11: Marker Allergens of Weed Pollen: Basic Considerations and Diagnostic Benefits in Routine Clinical Practice 240
11.1 Introduction 240
11.2 Allergen Nomenclature 242
11.3 Structure and Biological Function of Relevant Protein Families 242
11.3.1 Pectate Lyases 242
11.3.2 Defensin-Like Proteins 243
11.3.3 Nonspecific Lipid Transfer Proteins 244
11.3.4 Ole e 1-Like Proteins 244
11.4 Clinical Relevance of Allergens 244
11.4.1 Pectate Lyases 244
11.4.2 Defensin-Like Proteins 245
11.4.3 Nonspecific Lipid Transfer Proteins (nsLTP) 245
11.4.4 Ole e 1-Like Proteins 245
11.5 Sensitization Frequencies 245
11.6 Cross-Reactive Versus Marker Allergens 246
11.7 Allergy Diagnosis 248
11.8 Added Value of Molecular Allergy Diagnostics 248
11.9 Therapeutic Recommendations 250
11.10 Perspectives 250
11.11 Conclusions for Routine Clinical Practice 251
References 251
12: Molecular Diagnostics for Peanut Allergy 254
12.1 The Peanut’s Role as an Allergen 254
12.2 Individual Peanut Allergens 255
12.2.1 Primary Major Allergens: Storage Proteins 257
12.2.2 Primary Minor Allergens: Oleosins 257
12.2.3 Secondary Allergens: nsLTPs and Cross-Reactive Aeroallergens 258
12.3 Clinical Data Concerning Molecular Diagnostics 258
12.4 Diagnostics with Peanut Allergens 262
12.4.1 Available Single Allergens 262
12.4.2 Potential Benefits of Molecular Diagnostics with Peanut Allergens 262
12.4.3 Procedure for Diagnosing Peanut Allergy in Childhood (< 14 Years)
12.4.4 Common Peanut Cross-Reactions Regarding Birch Pollen Sensitization 265
12.4.5 Less Common Sensitization Patterns in Peanut Allergy 266
12.5 Cross-Reactive Allergens 266
12.6 Conclusions: Relevance in Daily Clinical Practice 266
References 267
13: Molecular Diagnostics for Tree Nut Allergy 270
13.1 Allergen Determination 270
13.2 Structure, Function, and Role of Allergens 272
13.3 Sensitization Frequencies 273
13.4 Serological Cross-Reactions 273
13.5 Diagnostics: Available Single Allergens 274
13.5.1 Hazelnut 274
13.5.2 Walnut 276
13.5.3 Other Nuts 278
13.6 Clinical Value of Molecular Diagnostics 278
13.7 Perspectives 279
13.8 Conclusions: Relevance in Daily Clinical Practice 279
References 281
14: Molecular Diagnostics of Allergy to Fruits and Vegetables 283
14.1 Introduction 283
14.2 Epidemiology of Fruit and Vegetable Allergy 284
14.3 Potential Benefits of Molecular Diagnostics in  Food Allergy 284
14.4 Allergies to Fruits and Vegetables: The Most Important Allergen Families 285
14.5 Molecular Diagnostics in Vegetable Allergy 286
14.5.1 Celery Root Allergy 286
14.5.2 Carrot Allergy 287
14.5.3 Tomato Allergy 288
14.6 Molecular Diagnostics in Fruit Allergy 289
14.6.1 Kiwi Fruit Allergy 290
14.6.2 Peach Allergy 294
14.6.3 Latex-Fruit Syndrome and the Relevance of the Hevein-­Like Domain 295
14.7 Summary and Outlook 295
14.8 Conclusion: Potential for Routine Clinical Practice 296
References 296
15: Cow’s Milk and Hen’s Egg Allergy: What Do Molecular-Based Allergy Diagnostics Have to Offer? 302
15.1 Introduction 302
15.2 Allergen Nomenclature 303
15.3 Properties of the Most Relevant Allergens 304
15.3.1 Cow’s Milk 304
15.3.2 Hen’s Egg 306
15.3.3 Special Case: Cow’s Milk and Hen’s Egg in Baked Foods 307
15.4 Prevalence, Distribution, and Prognosis of Sensitization 307
15.4.1 Prognosis 308
15.5 Diagnostic Methods 309
15.5.1 Assessing Clinical Relevance 309
15.5.2 Assessing Tolerance in Baked Goods 310
15.6 Additional Benefits Conferred by Molecular-Based Allergy Diagnostics 311
15.7 Treatment and Recommendations 311
15.8 Conclusions for Clinical Practice 312
References 312
16: Molecular and Extract-Based Diagnostics in Meat Allergy 315
16.1 Introduction to Molecular and Extract-Based Diagnostics in Meat Allergy 315
16.2 Pork-Cat Syndrome, a Link Between Pet Dander and Meat 316
16.2.1 Allergen Structure and Function 316
16.2.2 Allergen Prevalence and Sensitization 317
16.2.3 Diagnosis and Recommendations 318
16.3 Type I Hypersensitivity Reactions to Galactose-?-1,3-Galactose in Red Meat Allergy 319
16.3.1 Carbohydrate Side Chain Galactose-?-1,3-Galactose (?-Gal) 319
16.3.2 Type I Allergy to ?-Gal and the Role of Tick Bites 322
16.3.3 Diagnostic Measures in Delayed Type I Hypersensitivity Reactions to Red Meat and Innards 324
16.3.4 Clinical Relevance and Particular Features of Delayed Type I Hypersensitivity Reactions to Red Meat and Innards 324
16.4 Bird-Egg Syndrome and Genuine Poultry Meat Allergy 326
16.4.1 Types of Poultry Meat Allergy 326
16.4.2 Allergen Structure and Function 326
16.4.3 Allergen Prevalence and Sensitization in Bird-Egg Syndrome-Related Poultry Meat Allergy 327
16.4.4 Allergen Prevalence and Sensitization in Primary Poultry Meat Allergy 328
16.4.5 Immunologic Relationships Between Poultry Meat, Red Meat, and Other Foods 329
16.4.6 Diagnosis and Recommendations 330
16.5 Advantage of Molecular Diagnostics 331
16.6 Recommendations for Clinical Practice 331
References 332
17: Molecular Diagnostics in Food-­Dependent Exercise-Induced Anaphylaxis 337
17.1 Introduction 337
17.2 Allergen Identification 339
17.3 Structure, Function, and Importance of the Allergens 341
17.4 Sensitization Prevalences/Distribution 342
17.5 Cross-Reactive Versus Marker Allergens 343
17.6 Diagnostic Workup 344
17.7 Added Benefits Conferred by Molecular Allergy Diagnostics 346
17.8 Therapy and Recommendations 347
17.9 Perspectives 347
References 348
18: Benefits and Limitations of Recombinant Allergens in Diagnostics of Insect Venom Allergy 351
18.1 Introduction 351
18.2 Structure, Function, and Relevance of Hymenoptera Venom Allergens 354
18.3 Methodological Aspects for the Production of Recombinant Hymenoptera Venom Allergens 359
18.3.1 Recombinant Allergens from Eukaryotic Cells 359
18.4 Benefits of Molecular Diagnostics 360
18.4.1 Molecular Diagnostics for Differentiation of Double Sensitizations 360
18.4.2 Use of Recombinant Insect Venom Allergens in Clinical Routine Diagnostics 362
18.4.3 Improvement of Test Sensitivity by Recombinant Allergens 364
18.4.4 Potential Relevance for Specific Immunotherapy 366
18.5 Open Questions and Future Perspectives 367
18.6 Conclusion for Daily Practice 368
References 369
19: Molecular Diagnostics in Allergy to Mammals 373
19.1 Introduction 373
19.2 Protein Structure and Function 374
19.3 Current Status of Identified Allergenic Molecules from Different Mammalian Allergen Sources 375
19.3.1 Cat Allergenic Molecules 375
19.3.2 Dog Allergenic Molecules 376
19.3.3 Horse Allergenic Molecules 377
19.3.4 Cattle Allergenic Molecules 377
19.3.5 Rabbit Allergenic Molecules 378
19.3.6 Mouse and Rat Allergenic Molecules 378
19.3.7 Guinea Pig Allergenic Molecules 379
19.3.8 Hamster Allergenic Molecules 379
19.4 Prevalence of Sensitization/Distribution 379
19.5 Cross-Reactive Versus Marker Allergens in Mammals 380
19.6 Problems in Diagnosing Sensitization to Animals 381
19.7 Current Additional Benefits from Molecular Diagnostics 383
19.8 Therapy and Recommendations 383
19.9 Outlook 384
19.10 Conclusion: Potential for Routine Clinical Practice 384
References 386
20: Extract-Based and Molecular Diagnostics in Fish Allergy 390
20.1 Introduction 390
20.2 Allergens: Nomenclature 391
20.3 Allergens: Structure 391
20.4 Allergens: Function 394
20.5 Allergens: Relevance 395
20.6 Sensitization Prevalence 396
20.7 Cross-Reactive Versus Marker Allergens 397
20.8 Diagnostics 398
20.9 Additional Benefit from Molecular Diagnostics 399
20.10 Therapy and Recommendation 402
20.11 Outlook 402
20.12 Conclusions: Potential for Everyday Clinical Practice 403
References 403
21: Allergens and Molecular Diagnostics of Shellfish Allergy 407
21.1 Background 407
21.2 Classification of Shellfish Groups 408
21.3 Prevalence of Shellfish Allergy 409
21.4 Structure and Biological Functions of Shellfish Allergens 411
21.5 Clinical and Immunological Cross-Reactivity 415
21.5.1 Potential Advantages of Component-Resolved Diagnosis (CRD) in Shellfish Allergy 416
21.6 Diagnostics Separating IgE-Mediated Allergy from Other Reactions 417
21.7 Outlook for Future Diagnostic Options 418
21.8 Suggestions for Present Clinical Practice 418
References 420
22: Allergens, Diagnostics, and Therapeutic Aspects in House Dust Mite Allergy 423
22.1 Introduction 423
22.2 Designation of Allergens 424
22.3 Structure and Function of Allergens 424
22.4 Importance of the Allergens 428
22.5 Frequency of Sensitization/Distribution 429
22.6 Cross-Reactive Allergens/Marker Allergens 429
22.7 Diagnosis 430
22.8 Added Value of Molecular Diagnosis 431
22.9 Therapy and Recommendations 431
22.10 Perspectives 433
Conclusion 433
References 434
23: Cockroach, Tick, Storage Mite, and Other Arthropod Allergies: Molecular Aspects 437
23.1 Introduction 437
23.2 Cockroach Allergy 438
23.2.1 Exposure and Distribution 438
23.2.2 Allergen Identification 439
23.2.3 Function and Structure 440
23.2.4 Relevance and Sensitization Frequency 441
23.2.5 Cross-Reactive Allergens 441
23.3 Storage Mite Allergy 442
23.3.1 Exposure and Distribution 442
23.3.2 Allergen Identification 442
23.3.3 Relevance 442
23.3.4 Cross-Reactive Allergens 442
23.4 Tick Allergy 443
23.4.1 Exposure and Distribution 443
23.4.2 Allergen Identification 444
23.5 Allergies to Other Arthropods 444
23.6 Diagnostics and the Added Benefit of Molecular-Based Diagnosis 448
23.7 Treatment and Diagnostic Outlook 449
References 449
24: Mold Allergens and Their Importance in Molecular Allergy Diagnosis 453
24.1 Background 453
24.2 Classification of Fungal Allergens 454
24.3 Mold Exposure and Health Risks 454
24.4 Mold Allergens Belong to Various Protein Families, Most Often with Enzymatic Function in the Organism 458
24.4.1 Proteases 459
24.4.2 Ribosomal Proteins 459
24.4.3 Enolases 459
24.4.4 Dehydrogenases 459
24.4.5 Thioredoxins 460
24.4.6 Heat Shock Proteins 460
24.4.7 Peroxisomal Membrane Proteins 460
24.4.8 MnSODs 460
24.4.9 Flavodoxins 460
24.4.10 Cyclophilins 461
24.5 Commercially Available Single Allergens Originating from Mold 461
24.5.1 Specific IgG Tests 463
24.6 Outlook 463
24.7 Conclusions for Routine Clinical Practice 464
References 464
25: Latex Allergens: Source of Sensitization and Single Allergens 467
25.1 Introduction 467
25.2 Source of Proteins and Denomination of Allergens 468
25.3 Function of NRL Allergens 468
25.4 Importance of the Major Allergens 470
25.5 Dissemination of Latex Allergy 471
25.6 Cross-Reactive Carbohydrate Determinants (CCDs) 472
25.7 Latex-Food Syndrome 472
25.8 Diagnosis with Single Latex Allergens 474
25.9 Perspectives (Conclusions) 474
References 476
Part IV: Designer Allergens, Hypoallergens and Fusion Allergens 479
26: Recombinant Allergens in Specific Immunotherapy 480
26.1 Introduction 480
26.2 Advantages and Opportunities Posed by Recombinant Allergens for Allergen-Specific Immunotherapy 481
26.2.1 Recombinant Allergens for Specific Immunotherapy: Why? 481
26.2.2 The Challenge: Selecting the Relevant Allergens 482
26.2.3 Various Treatment Strategies Using Recombinant Allergens 484
26.3 Clinical Experience with Recombinant Allergens 485
26.3.1 Regulatory Requirements 485
26.3.2 Studies with Unmodified Recombinant Allergens 486
26.3.3 Studies with Hypoallergenic Recombinant Allergenoids 488
26.3.4 Studies Involving Alternative Concepts 490
26.4 Molecular Diagnosis for Molecular Treatment? 491
References 492
27: Definition and Design of Hypoallergenic Foods 494
27.1 Introduction 495
27.2 Definition of Hypoallergenic Foods 496
27.3 Design and Evaluation of Hypoallergenic Foods 497
27.4 Methods of Gene Silencing to Produce Hypoallergenic Foods 498
27.5 Allergen Reduction Achieved in Allergen Source Models of Plant-Based Foods 500
27.5.1 Rice (Oryza sativa) 500
27.5.2 Soybean (Glycine max) 502
27.5.3 Apple (Malus domestica) 503
27.5.4 Tomato (Solanum lycopersicum, Formerly: Lycopersicon esculentum) 504
27.5.5 Carrot (Daucus carota) 507
27.5.6 Peanut (Arachis hypogaea) 508
27.6 Acceptance of Hypoallergenic GM Foods Among Consumers 509
27.7 Additional Benefits of Molecular Diagnostics 510
27.8 Treatment and Recommendations 510
27.9 Perspectives 511
Conclusions 512
References 513
Index 519