Systemic Lupus Erythematosus Basic Applied and Clinical Aspects 1st edition by George Tsokos ISBN 0128020091 9780128019177

Part I. Epidemiology and Diagnosis

• Chapter 1. History of Systemic Lupus Erythematosus

• Chapter 2. The Patient

  • Improving Interactions with Your Patients

  • Improving Compliance

  • Common Pitfalls

  • Disability

  • Patient Education

  • The Lupus Secrets

• Chapter 3. Epidemiology

  • Summary

  • Introduction

  • Incidence and Prevalence

  • Factors that Affect the Course of SLE

  • Mortality and Survival in SLE

• Chapter 4. Measuring Disease Activity

  • Summary

• Chapter 5. Disease Development and Outcomes

  • Historical Perspective

  • Clinical Manifestations

  • Assessment of Disease Activity

  • Disease Damage

  • Patient-Reported Outcomes

  • Mortality

  • Causes of Death

  • Treatment Guidelines and Quality Indicators

  • Conclusions

• Chapter 6. Socioeconomic Aspects of Systemic Lupus Erythematosus

  • Summary

  • Definition and Measures of Socioeconomic Status

  • Problems with Measuring SES in Health Research

  • Impact of SES on Systemic Lupus Erythematosus Outcomes

  • Disease Activity

  • Damage Accrual

  • Disability

  • Mortality

  • Conclusions

• Chapter 7. Biomarkers in Systemic Lupus Erythematosus

  • Introduction

  • Biomarker Definition and Validation

  • Biomarkers for Diagnosis of SLE

  • Biomarkers for Measuring SLE Disease Activity

  • Biomarkers to Detect Specific Organ Involvement

  • Genetic Susceptibility and Theranostics

  • Conclusions

Part II. Pathogenesis

• Chapter 8. Overview of the Pathogenesis of Systemic Lupus Erythematosus

  • Genetic Predisposition

  • Epigenetic Contributions

  • Gender

  • Environment

  • Immune Abnormalities in SLE

  • Tissue Damage

  • Conclusions

• Chapter 9. Systemic Lupus Erythematosus and the Environment

  • Introduction

  • Infectious Agents, the Microbiome, and SLE

  • Cigarette Smoking and SLE

  • Exposure to Chemicals and Risk of SLE

  • Ultraviolet Radiation, Vitamin D, and SLE

  • Drugs, Vaccines, and SLE

  • Conclusion

• Chapter 10. Genes and Genetics in Human Systemic Lupus Erythematosus

  • Introduction

  • SLE-Risk Genes in Immunological Pathways

  • SLE-Risk Genes with Other Functions

  • Genes Connected to Phenotypes in SLE

  • Conclusion and Future Directions

• Chapter 11. Hormones

  • Sex Hormones

  • Hormones and the Immune Response

  • Hormone Receptors

  • Hormone Therapy

• Chapter 12. The Complement System in Systemic Lupus Erythematosus

  • Introduction

  • Complement Testing and its Interpretations

  • Immunology and Genetics of Early Complement Components of the Classical Pathway

  • Complement Receptors and Regulators in SLE

  • Autoantibodies to Complement and Acquired Deficiency of Complement in SLE

  • New Connections for Lupus and Complement

  • Conclusions

• Chapter 13. T Cells

  • Mechanisms through Which T Cells Promote SLE

  • Pro-inflammatory Activities

  • Signaling and Gene Expression in SLE T Cells

• Chapter 14. Integrating Current Thinking on Peripheral B-Cell Tolerance in Lupus

  • B-Cell Depletion Therapy, Regulatory B Cells, and Lupus

  • The Type I Interferon Pathway in Lupus and a Potential Link to Immune Tolerance

  • Complement Function, Apoptotic Cell Clearance, and Lupus

  • Increased BAFF in Lupus: A Contributor to a Break in Tolerance or Consequence of Inflammation?

• Chapter 15. Neutrophils in Systemic Lupus Erythematosus

  • Introduction

  • Neutrophil Dysfunction in SLE

  • NETosis in the Pathogenesis of SLE

  • Low-Density Granulocytes in SLE

  • DNA Methylation Changes in SLE Neutrophils and LDGs

  • Conclusion

• Chapter 16. The Role of Dendritic Cells in Systemic Lupus Erythematosus

  • Dendritic Cell Origins, Subsets, and Functions

  • DCs and SLE

  • Overall Picture of DC Implication in SLE Pathogenesis

  • Amplifying Mechanisms Promoting IFN-α Secretion in SLE and Activation of DCs

• Chapter 17. Cytokines

  • Cytokines in Systemic Lupus Erythematosus

  • IL-2

  • IL-17

  • IL-6

  • TNF

  • IFN-α

• Chapter 18. Toll-Like Receptors, Systemic Lupus Erythematosus

  • Toll-Like Receptor Family

  • TLR7

  • TLR8

  • TLR9

  • Conclusions

• Chapter 19. The Interferon System in Lupus Erythematosus

  • Introduction

  • The Interferon System

  • Activation and Regulation of Interferon Production

  • Effects of Interferons on the Immune System

  • Lupus and the Interferon System

  • Genes in Interferon Signaling Pathway and Lupus

  • Interferons in the Clinic

  • Conclusion

• Chapter 20. Humoral Pathogenesis: Fcγ Receptors in Autoimmunity and End-Organ Damage

  • Introduction

  • FcγRs: Structure and Function

  • IgG and FcγR Interactions

  • FcγRs and Complement

  • Activating and Inhibitory FcγR Signaling

  • Roles of FcγRs in SLE

  • Pathogenesis of Lupus Nephritis

  • Fcγ Receptor Polymorphisms and Copy Number Variation in Lupus

  • FcγR Targeted Treatments

  • Future Directions

• Chapter 21. Apoptosis, Autophagy, and Necrosis

  • Definition

  • Apoptosis

  • Autophagy

  • Necrosis

  • Concluding Remarks

• Chapter 22. Infections in Early Systemic Lupus Erythematosus Pathogenesis

  • Introduction

  • Pathogens Associated with Lupus Autoimmunity and Clinical Disease

  • Epstein–Barr Virus as a Model Infection in the Etiology of SLE

  • The Microbiome in Autoimmune Disease

  • Pathogen Exposures that May Protect against Lupus Autoimmunity

  • Conclusions

• Chapter 23. Origin of Autoantibodies

  • Summary

  • B-Cell Tolerance in SLE

  • Altered BCR Signaling in Lupus

  • Properties of Lupus Autoantibodies

  • GC versus Extrafollicular Origin of Autoantibodies

  • Role of TLR Signaling

  • Association of Autoantibodies with Accumulation of Intracellular Nucleic Acids

  • Relationship of IFN-I to Autoantibody Production

  • Association of Autoantibodies with Abnormal Clearance of Apoptotic Cells

  • Autoantibody Production Induced by Pristane

• Chapter 24. Anti-DNA Antibodies

  • Introduction

  • Cellular Source of Anti-DNA Antibodies

  • Contribution of Antigen Selection

  • Triggers: Chromatin and Environmental Exposures

  • Mechanisms of Injury in the Kidney and Brain

  • Immune Complexes and Myeloid Cell Activation

  • Summary

• Chapter 25. Antihistone and Antispliceosome Antibodies

  • Antihistone Antibodies

  • Antispliceosome Antibodies

• Chapter 26. Immune Complexes in Systemic Lupus Erythematosus

  • Basic Immunochemistry of Immune Complexes: The Precipitin Curve and Complement Activation

  • Immune Complexes and End-Organ Damage

  • Immune Complexes as Initiators and Regulator of the Autoimmune Response

  • Immune Complex Clearance and Localization

  • Autoantibodies to the Collagen-Like Region of C1q

  • Tissue Effects of Immune Complexes

  • Development of Therapies Based on Immune Complexes

  • Detection of Immune Complexes

  • Summary

• Chapter 27. MicroRNA in Systemic Lupus Erythematosus

  • Summary

  • Biology of miRNAs

  • Role of miRNAs in SLE

  • Conclusion

• Chapter 28. Oxidative Stress in Systemic Lupus Erythematosus: Causes, Consequences, and Treatment

  • Introduction

  • Accumulation of Dysfunctional Mitochondria Is the Source of Oxidative Stress in T Cells

  • Extramitochondrial Generation of Oxidative Stress

  • Oxidative Stress Due to Diminished Reducing Power

  • Biomarkers of Oxidative Stress Reflect Disease Activity in SLE

  • Oxidative Stress Is a Target for Treatment in SLE

• Chapter 29. Reactive Nitrogen Intermediates in the Pathogenesis of Systemic Lupus Erythematosus

  • Introduction

  • Biology of Reactive Intermediates

  • RNI in Murine Models of Lupus

  • Mechanisms of Increased iNOS Expression in Lupus

  • iNOS Inhibition in Murine Lupus

  • Potential Mechanisms for Pathogenicity of RNI in Murine Models of Lupus

  • Reactive Intermediates in Human Lupus

  • iNOS Expression in Proliferative Nephritis

  • Role of RNI in Vascular Disease in SLE

  • Pathogenic Mechanisms of RNI Production in Lupus Patients

  • Conclusion

• Chapter 30. Epigenetics

  • Introduction

  • DNA Methylation in T Cells from SLE Patients

  • Histone Modifications

  • Micro-RNAs in SLE

  • Molecular Mechanisms of Pathological Epigenetic Remodeling in SLE

  • Epigenetic Modification as Promising Targets for Future Treatment

  • Conclusions

• Chapter 31. What Do Mouse Models Teach Us about Human Systemic Lupus Erythematosus?

  • Commonly Used Murine Lupus Models

  • Murine Lupus Strains Constitute Excellent Models for Defining the Genetic Architecture of SLE

  • The Presence of Autoantibodies Is Not a Prerequisite for the Development of End Organ Damage

  • The Pathogenic Role of Leukocytes in Lupus

  • Macrophage: The Undefined Role of Macrophage Subtypes in SLE

  • DCs: Tipping the Balance from Immune Tolerance Toward Autoimmunity

  • Multiple Cytokines and Chemokines Also Contribute to Lupus Pathogenesis

  • Lessons from Therapeutic Studies in Murine Lupus Models

  • Concluding Thoughts

• Chapter 32. Genes and Genetics of Murine Systemic Lupus Erythematosus

  • Introduction

  • Mouse Models of Lupus Used in Genetic Studies

  • Predisposing Loci and Genes in Natural-Occurring Lupus Models

  • Lupus Predisposing Variants That Promote Lupus in Nonautoimmune Mice

  • Genes Affecting Susceptibility to End-Organ Pathology

  • Susceptibility Genes Affect Several Key Stages in Lupus Pathogenesis

  • Comparison with Human SLE Genes

  • Conclusion

Part III. Mechanisms of Tissue Damage

• Chapter 33. Mechanisms of Renal Damage in Systemic Lupus Erythematosus

  • Introduction

  • Histopathology of Lupus Nephritis

  • Mechanisms of Renal Damage in Lupus

  • Clinical Manifestations of Lupus Nephritis

  • Role of Inflammation and Immune Complexes in Renal Damage

  • Conclusion