Sjogren's syndrome : novel insights in pathogenic, clinical and therapeutic aspects / edited by Roberto Gerli ; co-edited by Elena Bartoloni, Alessia Alunno.

Format:

Book

Contributor:

Gerli, Robert.

Language:

English

Subjects (All):

Sjogren's syndrome.

Genre:

Electronic books.

Physical Description:

1 online resource

Place of Publication:

London, UK : Academic Press, 2016.

System Details:

text file

Summary:

Sjogren's Syndrome: Novel Insights in Pathogenic, Clinical and Therapeutic Aspects provides the reader with an overview of current knowledge about Sjogren's Syndrome. The book summarizes the huge amount of literature concerning related advances in genetic background, pathogenesis, clinical picture, and therapeutic approaches. It integrates basic immunology concepts, clinical aspects, and pharmacological issues. Scientific progress has allowed us to unmask novel pathogenic mechanisms, to perform genome wide studies, and to identify clinical and serological features associated with different disease subsets and, eventually, different disease prognoses. In addition, the increasing knowledge about SS pathogenesis provides the rationale to employ targeted therapies in SS as has already occurred in rheumatoid arthritis and systemic lupus erythematosus.

Contents:

1 Introduction: History of Sjögren's Syndrome / C. Baldini Baldini, C., S. Bombardieri Bombardieri, S.

1 Introduction 1

1.1 The History of Sjögren's Syndrome Before Henrik Sjögren 1

1.2 The History of Sjögren's Syndrome: Henrik Sjögren 3

1.3 The History of Sjögren's Syndrome: The Concept of Sjögren's Syndrome as an Autoimmune Disease 4

1.4 The History of Sjögren's Syndrome: Subsequent Milestones 5

References 7

2 Clinical Features / E. Bartoloni Bartoloni, E., A. Alunno Alunno, A., R. Gerli Gerli, R.

1 Introduction 11

2 The Many Facets of the Disease 11

3 Glandular Manifestations 16

4 Systemic Involvement 18

5 Nonspecific Manifestations 18

6 Periepithelial Manifestations 20

6.1 Lung 20

6.2 Kidney 22

6.3 Gastrointestinal Tract 22

6.4 Muscle 23

6.5 Nervous System 23

7 Immune Complex-Mediated Manifestations 24

7.1 Nervous System 24

7.2 Cutaneous Vasculitis 25

7.3 Lung 25

7.4 Kidney 26

8 Cardiovascular Manifestations 26

9 Conclusions 27

References 28

3 Management of Sjögren's Syndrome / C.P. Mavragani Mavragani, C.P., M.N. Manoussakis Manoussakis, M.N.

1 Introduction 35

2 Management of Glandular Complications 35

2.1 Dry Mouth and Salivary Gland Component 35

2.2 Dry Eyes 37

2.3 Other Glandular Manifestations 38

3 Management of Systemic Complications 39

3.1 Nonspecific Manifestations 39

3.2 Periepithelial Disease 41

4 Immune Complex-Mediated Disease 42

References 43

4 Classification Criteria for Sjögren's Syndrome / C. Vitali Vitali, C., N. Del Papa Papa, N. Del

1 General Concepts on Classification Criteria 47

2 The Historical Sets of Classification Criteria Proposed Before the 1990s 48

3 From the Preliminary European Criteria to the American-European Consensus Croup Criteria 51

4 The New Preliminary ACR Classification Criteria for Sjögren's Syndrome 54

5 Comparison of the New ACR Criteria With the AECG Classification Criteria 56

6 The ACR-EULAR Initiative 57

References 58

5 Imaging Procedures Useful for the Diagnosis of Sjögren's Syndrome: Abnormalities of the Major Salivary Glands / V. Devauchelle-Pensec Devauchelle-Pensec, V.

1 Sialography 61

1.1 Procedure 61

1.2 Validity for Sjögren's Syndrome 62

2 Sialoscintigraphy 62

2.1 Procedure 62

2.2 Validity for Sjögren's Syndrome 63

3 Ultrasonography 63

3.1 Procedure 63

3.2 Validity for Sjögren's Syndrome 63

4 Magnetic Resonance Imaging 66

4.1 Procedure 66

4.2 Validity for Sjögren's Syndrome 66

5 Elastometry 67

5.1 Procedure 67

5.2 Validity for Sjögren's Syndrome 67

6 FDG PET/CT Imaging 67

6.1 Procedure 67

6.2 Validity for SS 68

7 Conclusion 69

References 69

6 Sjögren's Syndrome-Associated Lymphoma / S. Gandolfo Gandolfo, S., L. Quartuccio Quartuccio, L., S. De Vita Vita, S. De

1 Introduction 73

2 Epidemiology and Histological Subtypes of Lymphoma in Sjögren's Syndrome 74

3 Predictors of Lymphoma in Sjögren's Syndrome 75

4 Lymphomagenesis in Primary Sjögren's Syndrome 78

4.1 The Classification of Sjögren's Syndrome-Related Lymphoprol iteration 78

4.2 Genetic Alterations in Sjögren's Syndrome-Related Lymphoma 79

4.3 The Role of infectious Triggers in Sjögren's Syndrome-Related Lymphoproliferation 79

4.4 Rheumatoid Factor Specificity of Sjögren's Syndrome-Related Lymphomas 80

4.5 Why Cryoglobulinemia Develops: Information From HCV-Related Cryoglobulinemia 81

4.6 Cryoglobulinemic Vasculitis in Sjögren's Syndrome: The Clinical Picture 82

4.7 Cryoglobulinemia Is More Related to MALT Lymphoproliferation in Sjögren's Syndrome 82

4.8 B-Cell Clonality in MALT Lymphoproliferation of Sjögren's Syndrome 83

4.9 Ectopic Germinal Center-Like Structures and Chemokines in Sjögren's Syndrome Salivary Glands 84

4.10 Molecular and Cellular Network in Salivary Glands With Lymphoproliferation 85

5 Biopsy and Imaging for an Improved Evaluation of Lymphoproliferation in Sjögren's Syndrome 87

6 Treatment 89

References 90

7 Spontaneous and Inducible Animal Models of Sjögren's Syndrome / E. Astorri Astorri, E., D. Lucchesi Lucchesi, D., C. Pitzalis Pitzalis, C., M. Bombardieri Bombardieri, M.

1 Spontaneous Models 99

1.1 NOD Mice 99

1.2 Other Spontaneous Models of SS: NZB and NZB/NZW F1, NFS/sId, IQI/Jic and MRL/+ and MRL/Ipr Mice 106

2 Inducible Models of SS-Like Sialadenitis and Autoimmunity 108

2.1 Immunization Methods to induce Sialadenitis 108

2.2 Virus-Induced Experimental Sialadenitis 109

References 113

8 Genetics, Genomics, Gene Expression Profiling, and Epigenetics in Sjögren's Syndrome / S.J. Bowman Bowman, S.J., B.A. Fisher Fisher, B.A.

1 Historical Background 119

2 Epidemiology, Prevalence, and Classification Criteria 120

3 Immunopathology of Sjögren's Syndrome 120

4 "Traditional" Genetics: Human Leukocyte Antigens 121

5 Candidate Gene Analysis 125

6 Genome-Wide Association Studies 125

7 Epigenetics 127

7.1 Gene Methylation and Other Processes 127

7.2 Micro-RNAs 129

8 Functional Genomics 129

8.1 Gene Expression Profiling: Interferon Signature 129

8.2 Genomics and Transcriptomics 131

8.3 Microbiotne Analysis 131

8.4 Proteomics 132

8.5 Metabolomics 133

9 Conclusions 133

Acknowledgments 134

References 134

9 Autoantigens and Autoantibodies in the Pathogenesis of Sjögren's Syndrome / E. Tinazzi Tinazzi, E., G. Patuzzo Patuzzo, G., C. Lunardi Lunardi, C.

1 Introduction 141

2 Pathogenesis and Autoantigens 143

2.1 Ro/SSA and La/SSB 143

2.2 Calreticulin 145

2.3 Muscarinic 3 Receptors 145

2.4 Carbonic Anhydrase II 146

2.5 α-Fodrin 146

2.6 Tear Lipocalin 147

3 Autoantibodies: Their Role in the Pathogenesis and Diagnosis 147

3.1 Antinuclear Antibodies and Anti-Ro/SSA and Anti-La/SSB 147

3.2 Rheumatoid Factor, Anticyclic Citrullinated Peptide Antibodies 149

3.3 Antibodies Against U1 Ribonucleoprotein 149

3.4 Anticentromere Antibodies 149

3.5 Antimitochondrial Antibodies 150

3.6 Anti-Smooth Muscle Antibodies 150

3.7 Antibodies Against Muscarinic Receptors Type 3 150

3.8 Autoantibodies Targeting Carbonic Anhydrase II 151

3.9 Antibodies Against α-Fodrin 151

4 Novel Proposed Autoantigens and Autoantibodies 151

5 Conclusions 152

References 153

10 Sjögren's Syndrome and Environmental Factors / S. Colafrancesco Colafrancesco, S., C. Perricone Perricone, C., Y. Shoenfeld Shoenfeld, Y.

1 Introduction 157

2 Sjögren's Syndrome and Infections 157

3 Sjögren's Syndrome and Vaccines 159

4 Sjögren's Syndrome and Silicone 160

5 Sjögren's Syndrome and ASIA Syndrome 163

6 Sjögren's Syndrome, Hormonal Factors, and Vitamin D 165

7 Sjögren's Syndrome, Stress, and Environmental Pollution 166

8 Conclusions 167

References 167

11 Histology of Sjögren's Syndrome / . Barone Barone, ., S. Colafrancesco Colafrancesco, S., J. Campos Campos, J.

1 Introduction 171

2 Salivary Gland Anatomy 171

3 Histology of Normal Salivary Glands 172

4 Salivary Gland Biopsy 173

5 Histological Findings in Salivary Glands From Sjögren's Syndrome Patients 174

6 Differential Diagnosis 175

7 Germinal Centers as Predictors of Lymphoma Development 177

8 Lymphoma Histopathology 180

9 The Value of Histopathological Assessment During Clinical Trials 180

10 Conclusions 182

References 182

12 Glandular Epithelium: Innocent Bystander or Leading Actor? / E.K. Kapsogeorgou Kapsogeorgou, E.K., A.C. Tzioufas Tzioufas, A.C.

1 Introduction 189

2 Dysfunction of Glandular Epithelia in Sjögren's Syndrome: "Innocent Bystanders"? 190

2.1 Altered Epithelial Secretory Function in Sjögren's Syndrome 190

2.2 Apoptotic Cell Death of Epithelial Cells in Sjögren's Syndrome 192

3 The Clinical Expression of "Autoimmune Epitheliitis" 193

4 Epithelium as the Leading Actor of Autoimmune Responses 193

4.1 Epithelial Cells Are Suitably Equipped to Mediate the Development and Perpetuation of SS Autoimmune Responses 193

4.2 Epithelial Cells Are Able to Mediate the Activation and Differentiation of Immune Cells 196

4.3 Epithelial Cells of Sjögren's Syndrome Patients Are Intrinsically Activated 197

5 Summary 197

Abbreviations 198

References 198

13 T Cells in the Pathogenesis of Sjögren's Syndrome: More Than Just Th1 and Th2 / A. Alunno Alunno, A., E. Bartoloni Bartoloni, E., R. Gerli Gerli, R.

1 Introduction 205

2 Regulatory T Cells in Sjögren's Syndrome 205

3 IL-17-ProducingT Cells in Sjögren's Syndrome 207

4 Follicular T Helper Cells in Sjögren's Syndrome 210

5 T Helper 22 and T Helper 9 Cells 210

6 Concluding Remarks 211

References 211

14 B Lymphocytes in Primary Sjögren's Syndrome / J.-O. Pers Pers, J.-O., P. Youinou Youinou, P.

1 B-Cell Hyperactivity Is a Hallmark of Primary Sjögren's Syndrome 217

2 B-Cell Classification According to Their Ontogenic State 218

3 B Lymphocytes in Salivary Glands 218

4 B Lymphocytes in Peripheral Blood 221

5 Intrinsic B-Cell Defects 222

6 Autoreactivity-Driven B Lymphocyte Proliferation 222

7 B-Cell-Derived Cytokines 223

8 Interconnections Between B- and T-Cell Cytokine Networks 223

9 Epigenetic Dysregulations in Salivary Glands Is Ascribed to B Cells 224

10 Conclusion 224

References 225

15 Cytokines, Chemokines, and the innate Immune System in Sjögren's Syndrome / S. Appel Appel, S., R. Jonsson Jonsson, R.

1 Introduction 229

2 Cytokines of the Innate Immune System in Primary Sjögren's Syndrome 230

2.1 Type I Interferon 230

2.2 Tumor Necrosis Factor 231

2.3 B-Cell Activating Factor 232

2.4 Interleukin-6 232

2.5 Interleukin-1 233

3 Conclusion 235

References 235

16 Autoantibodies and Autoantigens in Sjögren's Syndrome / R.I. Fox Fox, R.I., C.M. Fox Fox, C.M.

1 Background of Autoantibodies SSA/B 241

2 Methods of Detection of Antinuclear Antibodies and Ro/SSA and La/SSB 243

3 Detection of Specific Antibodies to Ro/SSA and La/SSB 245

4 Simple Model for the Role of Ro/SSA and La/SSB in Pathogenesis and as a Possible Target for Therapy 245

5 Mapping of Antigenic Epitopes on Ro/SSA and La/SSB 250

6 La/SSB Antibody 251

7 Antibody to Ro/SSA and CHB 251

8 Anti-Ro/SSA Antibodies Precede Development of Clinical Manifestations 252

9 Other Autoantibodies Associated With SS 252

10 Anti-α-Fodrin Antibodies 253

11 Antibodies to NA14 254

12 Nuclear Autoantigen 14kD 254

13 Summary 255

Abbreviations 257

References 257

17 Outcome Measures in Sjögren's Syndrome and Perspectives in Clinical Trial Design / R. Felten Felten, R., J. Sibilia Sibilia, J., J.-E.. Cottenberg Cottenberg, J.-E..

1 Current Outcome Measures in Primary Sjögren's Syndrome 263

1.1 Symptoms 263

1.2 Systemic Complications 264

1.3 Objective Assessment of Dryness (Tear and Saliva Secretion) 265

1.4 Other Potential Outcome Measures 267

2 Perspectives in Clinical Trial Design 267

2.1 Complexity of Designing a Clinical Trial in pSS 267

2.2 Perspectives for a New Composite Outcome Criteria 268

References 269

18 Novel Therapeutic Strategies in Sjögren's Syndrome: B-Cell Targeting / F. Carubbi Carubbi, F., P. Cipriani Cipriani, P., R. Giacomelli Giacomelli, R.

1 Therapeutic Potential for B-Cell Modulation in Sjögren's Syndrome 273

2 Anti-CD20 Antibodies in pSS Treatment: The Role of Rituximab 275

2.1 Clinical Effects of Rituximab in pSS 277

2.2 Retreatment and Safety 279

2.3 What Have We Learned About Rituximab From Clinical Trials in pSS? 280

3 Epratuzumab, an Anti-CD22 Antibody in pSS Treatment 281

4 Anti-B Lymphocyte Stimulator Therapy in pSS 282

4.1 Belimumab 282

5 Future Perspectives and Personalized Therapy 283

5.1 Inhibition of Lymphotoxin-β 283

5.2 Interleukin-6 Inhibition 284

5.3 B-/T-Cell Cooperation Interference 284

5.4 Potential Therapies Not Investigated in pSS 284

6 Conclusions 285

References 285

19 Novel Therapeutic Strategies in Sjögren's Syndrome: T-Cell Targeting / V.C. Kyttaris Kyttaris, V.C., G.C. Tsokos Tsokos, G.C.

1 Costimulation 291

1.1 CD28-B7 292

1.2 ICOS-B7RP1 293

1.3 CD154-CD40 294

2 T-Cell Trafficking 294

3 Cytokines 295

4 Conclusion 295

References 296

20 New Biological Avenues for Sjögren's Syndrome / R. Priori Priori, R., S. Colafrancesco Colafrancesco, S., C. Valesini Valesini, C., F. Barone Barone, F.

1 New Biological Treatments for Autoimmune Disease 299

2 The Interferon Signature 300

3 Innate Inflammatory Cytokines 301

4 T Cell Targeting 302

5 Tertiary Lymphoid Organ Development and the Role of Chemokines 304

6 Germinal Centers and Costimulatory Molecules 305

7 Intracellular Cascade Targeting 307

8 Regenerative Medicine for Sjögren's Syndrome 308

9 Conclusions 309

Acknowledgment 310

References 310.

Notes:

Description based on print version record.

Includes index.

ISBN:

012803632X

9780128036327

OCLC:

951807672

Access Restriction:

Restricted for use by site license.