Dubois' Lupus Erythematosus and Related Syndromes E-Book , livre ebook

Dubois’ Lupus Erythematosus and Related Syndromes
Expert Consult - Online and Print
Eighth Edition

Daniel J. Wallace, MD, FACP, FACR
Associate Director, Rheumatology Fellowship Program, Cedars-Sinai Medical Center, Clinical Professor of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California

Bevra Hannahs Hahn, MD
Chief, Rheumatology and Arthritis Professor of Medicine, Department of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California
Saunders
Table of Contents
Instructions for online access
Cover image
Title page
Copyright
Contributors
Preface
Section I: What is Lupus?
Chapter 1: Definition and Classification of Lupus and Lupus-Related Disorders
Systemic Lupus Erythematosus
Chronic Cutaneous Lupus
Drug-Induced Lupus Erythematosus
Mixed Connective Tissue Disease
Undifferentiated Connective Tissue Disease and Overlap Syndromes
Antiphospholipid Antibody Syndrome
Neonatal Lupus
Summary
Chapter 2: The Epidemiology of Lupus
The Fundamentals of Epidemiology
Pediatric Systemic Lupus Erythematosus
Cutaneous Lupus
Other Considerations
Environmental Epidemiology in Lupus
Conclusion
Section II: The Pathogenesis of Lupus
Chapter 3: The Pathogenesis of SLE
The Phases of Sle: Evolution of Disease in Susceptible Persons
Overview: The Major Immune Pathways Favoring Autoantibody Production
Current Approved and Investigational Therapies for SLE
Chapter 4: Genetics of Human SLE
Monogenic Deficiencies and Rare Mutations with SLE
Polygenic Common Variants in SLE
Gene-Gene Interactions among Susceptibility Loci in SLE
Common Loci among Autoimmune Diseases
Conclusion
Chapter 5: Epigenetics of Lupus
DNA Hypomethylation in SLE
Histone Modification Changes in SLE
microRNAs in SLE
Conclusions and Future Perspectives
Chapter 6: The Innate Immune System in SLE
What Constitutes an Autoantigen?
The Endosomal Nucleic Acid–Sensing PRRs
TLR7 and TLR9 in SLE
In Vivo Support for TLR Associations with SLE
Potential Sources of Autoantigen
The Cytosolic Nucleic Acid–Sensing PRRs
Defects in DNA and RNA Degradation
Summary and Potential Therapies: Implication for Targeting PRR Pathways
Chapter 7: Cytokines and Interferons in Lupus
Properties of Cytokines and Their Receptors
Assessment of Cytokine Production
Use of Microarray to Study Cytokine Effects
Activation of the Immune Response in SLE
Cytokines of the Innate Immune Response
Cytokines of the Adaptive Immune Response
Summary
Chapter 8: The Structure and Derivation of Antibodies and Autoantibodies
Structure of the Antibody Molecule
Antibody Assembly
Generation of Antibody Diversity
Somatic Hypermutation
B-Cell Subsets: Implications for SLE
Toll-Like Receptors in B-Cell Function
Pathogenic Autoantibodies
Genetic and Molecular Analysis of Anti-DNA Antibodies
Autoantibody Induction
B-Cell Tolerance
Therapeutic Interventions
Non–Antigen-Specific Therapies
Antigen-Based Therapies
Summary
Chapter 9: T Cells
Role of T Cells in Autoimmunity and Inflammation
Intrinsic T-Cell Defects
Conclusion
Chapter 10: Regulatory Cells in SLE
Regulatory T Cells
Regulatory B Cells
Myeloid-Derived Suppressor Cells
Dendritic Cells
Natural killer Cells
Invariant NKT cells
Conclusions
Chapter 11: Apoptosis, Necrosis, and Autophagy
Definitions
Biochemistry of Apoptosis
Initiation and Pathways of Apoptosis
Removal of Apoptotic Cells
Apoptosis Abnormalities in Human SLE
Conclusions
Acknowledgments
Chapter 12: Abnormalities in Immune Complex Clearance and Fcγ Receptor Function
The Role of the Mononuclear Phagocyte System in the Clearance of Immune Complexes
Mechanisms of Immune Complex Clearance
Abnormal Immune Complex Clearance in SLE
Biology of Human Fcγ Receptors
Abnormalities in Fcγ Receptors in SLE
Strategies for Modulating FcγR-Mediated Immune Complex Clearance and Receptor Function
Acknowledgments
Chapter 13: Neural-Immune Interactions: Principles and Relevance to SLE
The Immune System
Central Nervous System Regulation of Immunity
Physiologic Impact of Miscommunications between the CNS and Immune System
Summary
Chapter 14: Complement and SLE
Historical Overview
Biology of the Complement System
Complement and SLE
Analyses of Complement
Soluble Complement Components as Biomarkers for SLE
Cell-Bound Complement as a Biomarker for SLE
Anticomplement Therapeutics for SLE
Conclusion
Chapter 15: Mechanisms of Acute Inflammation and Vascular Injury in SLE
Epidemiology of Premature Vascular Damage in SLE
Subclinical and Clinical Vascular Damage in SLE
Mechanisms of Atherosclerosis Development in the General Population
Mechanisms of Endothelial Inflammation, Injury, and Atherosclerosis in SLE
Conclusion
Chapter 16: Mechanisms of Tissue Damage—Free Radicals and Fibrosis
Free Radicals and Oxidative Stress
Fibrosis in SLE
Conclusion
Chapter 17: Animal Models of SLE
Clinical Disease, Autoantibodies, Immunologic Abnormalities, and Genetics in Spontaneous Multigenic Murine SLE
Induction of Lupus in Normal Mouse Strains
Murine Lupus Models Used to Test Therapeutic Interventions
Lupus in Domestic Animals
Use and Analysis of Animal Strains for Lupus Research
Chapter 18: Pathogenetic Mechanisms in Lupus Nephritis
Renal Anatomy and Physiology
Mechanisms for Immune Complex Deposition in the Kidneys
Pauci-Immune Glomerulonephritis
Mouse Models of Lupus Nephritis
Kidney Effector Mechanisms
Progression to Fibrosis and Sclerosis
Systems Biology of Lupus Nephritis: Harnessing Molecular Medicine to Define Regulatory Networks in Lupus Nephritis
Future Directions in SLE Nephritis
Section III: Autoantibodies
Chapter 19: Immune Tolerance Defects in Lupus
Immune Tolerance
Immune Tolerance Defects in Lupus
Strategies to Reestablish Tolerance in Lupus
Synthesis
Chapter 20: Autoantibodies
Antibody Structure and Function
Antibody Production and the Generation of Diversity
Anti-DNA Antibodies in Lupus: Historical Overview
Measurement of Anti-dsDNA Antibodies
Work from Experimental Models Emphasing the Potential Importance of Anti-dsDNA Antibodies
How Pathogenic Anti-dsDNA Antibodies Bind to Tissues: The Importance of Binding to Nucleosomes
Cross-Reaction of Anti-DNA Antibodies with Intracellular Antigens
Structure and Origin of Pathogenic Anti-dsDNA and Antinucleosome Antibodies
Can Measuring Anti-dsDNA Levels Help Us Manage Patients with SLE?
Summary
Anti–Endothelial Cell Antibodies
Antigenic Specificity and Methods of Detection of Anti-C1q
Clinical Associations
Do Levels of Anti-C1q Follow Disease Activity in Lupus (Nephritis)?
Pathogenic Role of Anti-C1q Autoantibodies
Conclusion
Structure of the Antigens
Assays for Measuring Anti-ENA Antibodies
Prevalence and Clinical Associations in SLE
Virus Infections as Triggers for Autoimmunity
Sequential Presentation of Anti-ENA Antibodies and Relationship of Anti-ENA to Other Lupus-Specific Autoantibodies
Role of Apoptosis for the Generation of Anti-ENA Antibodies
Toll-Like Receptors as Key Molecules for the Generation of Anti-ENA Antibodies
Genetic Risks and Anti-ENA Antibodies
Pathogenic Importance of Anti-RNP and Anti-Sm Antibodies
Pathogenic Role of Anti-Ro/SSA and Anti-La/SSB Antibodies
Chapter 21: Autoantigenesis and Antigen-Based Therapy and Vaccination in SLE
Autoantigenesis: Mechanisms that Make an Antigen an Autoantigen
Mechanisms by which Autoantigens May Contribute to the Development of Disease
Common Autoantigens in Lupus
Identification of Autoantigenic Epitopes in Lupus
Autoantigen-Based Vaccination and Peptide Therapies in Lupus
Mechanisms of Peptide-Based Therapies in Lupus
Will Peptide-Specific Treatment Ever Be a Reality in Patients with SLE?
Synthesis
Section IV: Clinical Aspects of SLE
Chapter 22: Overview and Clinical Presentation
History
Chief Complaint
Variations in Clinical Presentation
Constitutional Symptoms
Chapter 23: Pathomechanisms of Cutaneous Lupus Erythematosus
Clinical Photosensitivity in Lupus
Responses to Ultraviolet Light in Cutaneous Lupus Erythematosus
Humoral Factors in Cutaneous Lupus Erythematosus
Cellular Factors
Cofactors in Cutaneous Lupus Erythematosus
A Model of Pathogenesis of Cutaneous Lupus Erythematosus
Acknowledgments
Chapter 24: Skin Disease in Cutaneous Lupus Erythematosus
History
Epidemiology
Triggers of CLE
Clinical Features
Pathology
Immunopathology
Laboratory Findings
Differential Diagnosis
Treatment
Lupus-Nonspecific Skin Lesions
Photosensitivity
Alopecia
Cutaneous Vascular Reactions
Other LE-Nonspecific Skin Lesions
Conclusion