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Molecular Allergy Diagnostics - Innovation for a Better Patient Management
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Molecular Allergy Diagnostics - Innovation for a Better Patient Management
von: Jörg Kleine-Tebbe, Thilo Jakob
Springer-Verlag, 2017
ISBN: 9783319424996
537 Seiten, Download: 13568 KB
 
Format: PDF
geeignet für: PC, MAC, Laptop Online-Lesen Apple iPad, Android Tablet PC's

Typ: B (paralleler Zugriff)

 

 
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Inhaltsverzeichnis

  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) 263  
           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  


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