Primary Immunodeficiency Diseases (eBook)

Dedication 5
Foreword 7
Preface 9
Contents 11
Contributors 19
Abbreviations 25
An Introduction to Primary Immunodeficiency Diseases 30
Core Messages 30
1.1 Definition 30
1.2 Etiology 31
1.3 Clinical Manifestations 43
1.4 Diagnosis 49
1.5 Management 54
References 59
Combined T and B Cell Immunodeficiencies 68
Core Messages 68
2.1 Introduction 68
2.2 T- B+ Severe Combined Immunodeficiency 71
2.3 T- B- Severe Combined Immunodeficiency 77
2.4 Omenn Syndrome 82
2.5 DNA Ligase IV Deficiency 83
2.6 Cernunnos Deficiency 84
2.7 Purine Nucleoside Phosphorylase (PNP) Deficiency 85
2.8 Immunoglobulin Class Switch Recombination Deficiencies ( affecting CD40 – CD40L) 88
2.9 MHC Class II Deficiency 91
2.10 MHC Class I Deficiency 94
2.11 CD8 Deficiency 97
2.12 CD4 Deficiency 99
2.13 CRAC Deficiency 101
2.14 Winged-Helix-Nude ( WHN) Deficiency 102
2.15 CD25 Deficiency 103
2.16 STAT5B Deficiency 105
References 107
Predominantly Antibody Deficiencies 126
Core Messages 126
3.1 Introduction 126
3.2 Agammaglobulinemia with Absent B Cells 128
3.3 Hypogammaglobulinemia with Normal/ Low Number of B Cells (Common Variable Immunodeficiency, ICOS Deficiency, TACI Deficiency, CD19 Deficiency, Other Forms of Hypogammaglobulinemia) 134
3.4 Immunoglobulin Class Switch Recombination Deficiencies ( Due to Intrinsic B Cell Defects) 140
3.5 Selective IgA Deficiency 142
3.6 Other Immunoglobulin Isotypes or Light Chain Deficiencies (Isolated IgG Subclass Deficiency, IgA with IgG Subclass Deficiency, Ig Heavy Chain Deletions, k Light Chain Deficiency) 145
3.7 Specific Antibody Deficiency with Normal Immunoglobulin Concentrations 146
3.8 Transient Hypogammaglobulinemia of Infancy 147
References 148
Phagocytes Defects 160
Core Messages 160
4.1 Introduction 160
4.2 Severe Congenital Neutropenias 160
4.3 Cyclic Neutropenia 164
4.4 Leukocyte Adhesion Deficiency 165
4.5 RAC-2 Deficiency 170
4.6 b-Actin Deficiency 170
4.7 Chronic Granulomatous Disease ( CGD) 172
4.8 Neutrophil G-6PD Deficiency 181
4.9 Myeloperoxidase Deficiency 182
4.10 Specific Granule Deficiency 183
4.11 Shwachman–Diamond Syndrome 184
4.12 Localised Juvenile Periodontitis 187
4.13 Papillon–Lefèvre Syndrome 187
References 188
Genetic Disorders of Immune Regulation 196
Core Messages 196
5.1 Introduction 196
5.2 Familial Hemophagocytic Lymphohistiocytosis (Perforin Deficiency, MUNC13-4 Deficiency, Syntaxin 11 Deficiency) 197
5.3 Immunodeficiency with Hypopigmentation (Chediak-Higashi Syndrome, Griscelli Syndrome, Type II, Hermansky-Pudlak Syndrome, Type II, p14 Deficiency) 201
5.4 X-Linked Lymphoproliferative Syndrome (XLP) (SAP Deficiency, XIAP Deficiency) 204
5.5 Autoimmune Lymphoproliferative Syndrome (ALPS) (ALPS Ia, Ib, IIa, IIb, III) 207
5.6 Autoimmune Polyendocrinopathy with Candidiasis and Ectodermal Dystrophy ( APECED) 211
5.7 Immunodysregulation, Polyendocrinopathy, Enteropathy, X- Linked ( IPEX) 213
References 216
Defects in Innate Immunity: Receptors and Signaling Components 224
Core Messages 224
6.1 Introduction 224
6.2 Defective Toll-Like Receptor (TLR) Signaling Without Ectodermal Dysplasia (IRAK-4 Deficiency, TLR3 Deficiency, UNC-93B Deficiency) 225
6.3 Defective Toll-Like Receptor (TLR) Signaling with Ectodermal Dysplasia (XL- and AD-Anhidrotic Ectodermal Dysplasias with Immunodeficiency) 228
6.4 Mendelian Susceptibility to Mycobacterial Diseases (IFN- g Receptor 1/2 Deficiencies, IL-12/23 Receptor b1 Chain Deficiency, IL-12p40 Deficiency, STAT1 Deficiency, LZ-NEMO Deficiency) 230
6.5 Warts, Hypogammaglobulinemia, Infections, Myelokathexis ( WHIM) Syndrome 234
6.6 Epidermodysplasia Verruciformis (EV Types 1,2) 236
References 237
Autoinflammatory Disorders 244
Core Messages 244
7.1 Introduction 244
7.2 Familial Mediterranean Fever (FMF) 246
7.3 Mevalonate Kinase Deficiency (MKD) (Hyperimmunoglobulinemia D and Periodic Fever Syndrome, Mevalonic aciduria) 249
7.4 Tumor Necrosis Factor Receptor-Associated Periodic Syndrome ( TRAPS) 250
7.5 Cryopyrin-Associated Periodic Syndrome (CAPS) (Chronic Infantile Neurological Cutaneous Articular Syndrome, Muckle–Wells Syndrome, Familial Cold Autoinflammatory Syndrome) 252
7.6 Blau Syndrome 253
7.7 Pyogenic Arthritis, Pyoderma Gangrenosum and Acne Syndrome (PAPA) 254
7.8 Multifactorial/Polygenic Autoinflammatory Diseases 255
References 257
Complement Deficiencies 264
Core Messages 264
8.1 Introduction 264
8.2 Deficiencies of Classical Pathway Components (C1q/C1r/C1s Deficiencies, C4 Deficiency, C2 Deficiency) 267
8.3 Deficiencies of Lectin Pathway Components (MBL Deficiency, MASP2 Deficiency) 268
8.4 Deficiencies of Alternative Pathway Components (Factor D Deficiency, Properdin Deficiency) 269
8.5 Deficiency of Complement Component C3 270
8.6 Deficiencies of Terminal Pathway Components (C5-9 Deficiencies) 271
8.7 Deficiencies of Complement Regulatory Proteins (C1 Inhibitor Deficiency, Factor I Deficiency, Factor H Deficiency, CD46 Deficiency, CD55 Deficiency, CD59 Deficiency) 272
References 275
Other Well-Defined Immunodeficiencies 280
Core Messages 280
9.1 Introduction 280
9.2 Other Syndromes Associated with 281
Defective DNA Repair 281
9.3 Di George Syndrome 287
9.4 Wiskott-Aldrich Syndrome 291
9.5 Hyper-IgE Syndrome 296
9.6 Immuno- Osseous Dysplasias 298
9.7 Chronic Mucocutaneous Candidiasis 301
9.8 Netherton Syndrome 303
9.9 Dyskeratosis Congenita and Høyeraal- Hreidarsson Syndrome 305
References 307
Syndromic Immunodeficiencies 320
Core Messages 320
10.1 Introduction 320
10.2 Syndromes Associated with Growth Deficiency 322
10.3 Syndromes Associated with Gastrointestinal Dysfunction 325
10.4 Syndromes Associated with Cutaneous Abnormalities 327
10.5 Syndromes Associated with Neurologic Dysfunction 329
10.6 Inborn Errors of Metabolism Associated with Immunodeficiency 330
10.7 Syndromes with Chromosome Instability and/ or Defective DNA Repair Associated with Immunodeficiency 332
10.8 Syndromes Associated with Chromosomal Abnormalities of Number or Structure 334
References 336
Treatment of Primary Immunodeficiency Diseases 344
Core Messages 344
11.1 Introduction 344
11.2 Therapy for Combined T and B Cell Immunodeficiencies 344
11.3 Therapy for Predominantly Antibody Deficiencies 347
11.4 Therapy for Phagocytes Defects 350
11.5 Therapy for Genetic Disorders of Immune Regulation 352
11.6 Therapy for Defects in Innate Immunity: Receptors and Signaling Components 354
11.7 Therapy for Autoinflammatory Disorders 354
11.8 Therapy for Complement Deficiencies 355
11.9 Therapy for Other Well-Defined Immunodeficiencies 355
References 358
Index 364