Preface xxiii
Part I Biological Basics 1
1 Innate Immune Defence 3
Margot Lepage and Valerie Dubois
1.1 Introduction 3
1.2 Anatomical Barriers and Initial Chemical Defenses 3
1.3 The Complement System 6
1.4 Danger Recognition 8
1.5 Inflammatory Reaction and Effector Cells of the Innate Immune Response 16
1.6 Bridging Innate and Adaptive Immunity 27
1.7 Conclusion 29
1.8 Perspective: The Concept of Trained Immunity 31
Abbreviations 32
References 35
2 Specific Immune Defence 39
Eric Spierings
2.1 Introduction 39
2.2 Components of the Adaptive Immune System 40
2.3 The Major Histocompatibility Complex and Adaptive Immune Responses 43
2.4 T Cell-Mediated Immune Response 47
2.5 B Cell-Mediated Immune Response 52
2.6 Receptors of the Specific Immune System 58
2.7 Immunological Memory 62
2.8 Conclusion/Summary/Future 64
References 65
3 The HLA/MHC System 69
Neema Mayor and James Robinson
3.1 Introduction 69
3.2 IPD-IMGT/HLA Database 82
3.3 Limits to HLA Variation 83
3.4 Summary 84
References 84
4 The HNA System 89
Anthony Poles
4.1 Neutrophils and Associated Functions 89
4.2 Human Neutrophil Antigens (HNA) 90
4.3 Clinical Conditions Associated with HNA Specific Antibodies 96
References 98
5 Natural Killer Cell Receptors 101
Dianne De Santis and Lucy Sullivan
5.1 Introduction 101
5.2 NK Cells 101
5.3 “Missing Self” Hypothesis and Hybrid Resistance 102
5.4 NK Cell Receptors 103
5.5 Killer Immunoglobulin-Like Receptors (KIRs) 104
5.6 CD94-NKG2 Receptors 113
References 119
6 The HPA System 127
Romy Pothof, Leendert Porcelijn, and Masja de Haas
6.1 Platelet Antigens 127
6.2 Human Platelet Antigens 127
References 131
7 Other Polymorphic Systems 133
Hana Rohn and Vera Rebmann
7.1 Introduction 133
7.2 The Structure of HLA-like MICA and MICB Molecules 133
7.3 The Functions of HLA-like MICA and MICB Molecules 134
7.4 The Expression of HLA-like MICA and MICB Molecules 134
7.5 The Polymorphisms of HLA-like MICA and MICB Molecules and Functional Consequence 135
7.6 Nonclassical HLA Class I 136
7.7 Key Differences Between Nonclassical HLA Class I and Classical HLA Class I Molecules 136
7.8 The Expression of HLA-E Molecules 137
7.9 The HLA-E Peptide Presentation Controls the Functional Interaction with NK and T Cells 137
7.10 The Polymorphisms of HLA-E and Its Influence on Gene Expression 139
7.11 The Expression of HLA-G 139
7.12 The Unique Structural Features of HLA-G 140
7.13 The Functions of HLA-G are Directed by the Structural Features 141
7.14 The Polymorphisms of HLA-G and Its Impact on Gene Expression 142
7.15 The Expression of HLA-F 143
7.16 The Functions of HLA-F are Directed by Its Structural Features 144
7.17 The Polymorphisms of HLA-F and Its Impact on Gene Expression 144
7.18 Summary 145
References 147
Part II Clinical Applications 155
8 Basic Concepts of Organ Transplantation 157
Ilias Doxiadis and Claudia Lehmann
8.1 Introduction 157
8.2 Overview of the Decision-Making Procedure 158
8.3 Registration and Waiting List 159
8.4 Procurement of the Organs 161
8.5 Postmortem Allocation 163
8.6 The Crossmatch 166
8.7 Prospective Outlooks 167
References 168
9 Basic Concepts of Organ Rejection 171
Volker Oberle and Melanie Gerth
9.1 Introduction 171
9.2 The Immune System: Balancing Self and Foreign Recognition 171
9.3 Antigens: Self and Foreign? 172
9.4 Immune Tolerance: Maintaining the Balance 172
9.5 Autoimmunity 173
9.6 Foreign Recognition Leading to Rejection 173
9.7 GvHD 175
9.8 Conclusion 175
References 177
10 Treatment of Organ Rejection 179
Marie Dirix, Britt Ceuleers, and Johan W. De Fijter
10.1 Introduction 179
10.2 Prevention of Rejection: Induction and Maintenance Immunosuppression 180
10.3 Treatment of Rejection 192
10.4 Conclusions 198
References 198
11 Stemcell Transplantation 209
Effie W. Petersdorf
11.1 State-of-the-Art of Allogeneic Hematopoietic Cell Transplantation 209
11.2 Haploidentical HCT 212
11.3 Immunobiology of Haploidentical Related Donor Transplantation 215
11.4 Selection of Related Donors for Transplantation: Non-HLA Factors 229
11.5 Concluding Remarks 231
References 232
12 Stemcell Transplantation from Unrelated Donors 251
Volker Oberle
12.1 Introduction 251
12.2 The Search for Unrelated Donors 251
12.3 Laboratory Work 254
12.4 Clinical Outcomes of Unrelated Stem Cell Transplantation 257
12.5 Challenges in Unrelated Stem Cell Transplantation 257
12.6 Future Directions and Emerging Technologies 258
12.7 Conclusion 258
References 258
13 Chimerism Testing in Stem Cell Transplantation 263
Andreas Heinold
13.1 Introduction 263
13.2 Methods for Molecular Genetic Chimerism Testing 264
13.3 Sensitivity of Molecular Genetic Chimerism Testing 270
13.4 Choice of Markers for Quantification 271
13.5 Chimerism Testing for Nonmalignant Disorders 272
13.6 Reporting Chimerism 272
13.7 Time Course of Chimerism Analyses 273
13.8 Advantages and Disadvantages of Highly Sensitive Chimerism Testing 275
13.9 Cell Sources for Identifying Recipient- and Donor-Specific Markers 275
13.10 Cell Sources for Chimerism Monitoring 276
13.11 Intervals for Chimerism Testing 276
13.12 Chimerism-Related Diagnostics 277
References 279
14 Disease Associations with HLA Alleles 285
Eduard Palou
14.1 HLA and Disease Association 285
14.2 Mechanisms of HLA and Disease Associations 286
14.3 Autoimmune Diseases Associated with HLA 289
14.4 Other Diseases Associated with HLA 295
14.5 Laboratory Diagnostics 298
14.6 Concluding Remarks 299
References 300
15 Drug Associations with HLA Alleles 303
Melanie Gerth and Thomas M. C. Binder
15.1 Introduction 303
15.2 Classification of Drug Hypersensitivity Syndromes 304
15.3 Immunopathogenesis of Drug Hypersensitivity Syndromes 307
15.4 HLA and Hypersensitivity Reactions 310
15.5 Clinical Implications of HLA Testing 321
15.6 Future Directions 323
15.7 Conclusion 323
References 324
16 Diseases in the Field of Transfusion Medicine 333
Andrea Bontadini, Roberto Crocchiolo, and Luca Mascaretti
16.1 Introduction 333
16.2 Platelet Transfusion Refractoriness 334
16.3 Transfusion-Related Adverse Events 340
16.4 Neonatal Alloimmune Neutropenia 345
16.5 Fetal and Neonatal Alloimmune Thrombocytopenia 347
16.6 Conclusions 349
References 349
Part III Methods in Immunogentics and Histocompatibility 359
17 Isolation and Purification of Test Material 361
Ingrid Fae
17.1 DNA Extraction 361
17.2 RNA Extraction 365
17.3 cfDNA Extraction 366
17.4 Cell Preparation 368
Abbreviations 372
References 372
18 HLA-Antibody Determination 375
Stefan Schaub, Caroline Wehmeier, and Gideon Honger
18.1 Overview and Characteristics of Different HLA Antibody Detection Assays 375
18.2 The Multiplex Bead Array Platform (Luminex®) 379
18.3 Additional Methods/Tools 387
References 393
19 Low/Medium-Resolution HLA Typing 399
Milena Ivanova and Velizar Shivarov
19.1 Introduction 399
19.2 Cellular and Serological Tests for HLA Typing 400
19.3 DNA-based Methods for HLA Low-Resolution Typing 401
References 408
20 High-Resolution HLA Typing 413
EH Rozemuller and W. Mulder
20.1 Introduction 413
20.2 HLA Genes 414
20.3 PCR Amplification 414
20.4 Gene Capture Method 417
20.5 SBT by Sanger Sequencing 417
20.6 HLATypingbyNGSSBT 419
20.7 HLA Typing by Short-read Sequencing 421
20.7.1 Paired-end Sequencing 423
20.8 HLA Typing by Long-read Sequencing 424
20.9 Ambiguities 425
20.10 Phasing 427
20.11 Data Analysis 429
20.12 Special Cases 437
Abbreviations 439
References 440
21 Crossmatching in Transplantation 443
Melanie Gerth and Volker Oberle
21.1 Introduction 443
21.2 The Mechanism of Crossmatching 444
21.3 Crossmatch Methods 444
21.4 Summary 452
References 453
22 Determination of Antibodies and Typing in the HPA System 455
Volker Kiefel
22.1 Introduction to Platelet Antibody and Antigen Testing 455
22.2 Principles of Antibody Testing 455
22.3 Additional Techniques 457
22.4 Protocol: Platelet Suspension Immunofluorescence Test 458
22.5 Protocol: Isolation of Platelets for Serological Testing 459
22.6 Protocol: Monoclonal Antibody Immobilization of Platelet Antigens Assay (MAIPA) 460
22.7 New Developments for Platelet Antibody Detection 464
22.8 HPA-Antigen Testing 464
22.9 Concluding Remarks 465
References 466
23 KIR Genotyping 469
Dianne De Santis, Katherine M. Kichula, and Paul J. Norman
23.1 Complexity of KIR Genomic Region 469
23.2 KIR Genotyping 471
References 479
24 Determination of Antibodies and Typing in the HNA System 485
Anthony Poles
24.1 Introduction to Granulocyte Antibody and Antigen Testing 485
24.2 Principles of Antibody Testing 485
24.3 HNA Typing Techniques 490
References 491
25 Determination and Typing of Other Polymorphic Systems 495
Falko M. Heinemann, Vera Rebmann, and Rafael Tomoya Michita
25.1 Introduction 495
25.2 MICA/B Allele Typing Methods 495
25.3 MICA/B Single Nucleotide Variant Genotyping Methods 508
25.4 HLA-G Allele Typing Methods 508
25.5 HLA-E Typing Methods 515
25.6 HLA-F Typing Methods 518
25.7 Technical Aspects for the Detection of Anti-MICA Antibodies in Transplantation Patients 521
References 523
Part IV Regulatory Aspects 535
26 Regulations in Histocompatibility and Immunogenetics: Accreditation, External Proficiency Testing, Quality Management 537
Eduard K. Petershofen, Andrea Harmer, and Luca Mascaretti
26.1 Introduction 537
26.2 Legal Requirements 537
26.3 National Guidelines 538
26.4 Standards 538
26.5 Elements of Quality Management Systems 540
26.6 Practical Considerations for a QMS 540
26.7 Licensing, Accreditation, and Certification 544
26.8 EFI Accreditation Program 545
26.9 ISO Standards 546
26.10 Future Perspectives 547
Table of Acronyms and Abbreviations 548
References 549
Index 561
