Systemic Lupus Erythematosus
Basic, Applied and Clinical Aspects
- 1st Edition - December 23, 2015
- Editor: George C. Tsokos
- Language: English
- eBook ISBN:9 7 8 - 0 - 1 2 - 8 0 2 0 0 9 - 8
Systemic Lupus Erythematosus combines basic science with clinical science to provide a translational treatment of the disease and is a useful reference for specialists in the diagn… Read more
Systemic Lupus Erythematosus combines basic science with clinical science to provide a translational treatment of the disease and is a useful reference for specialists in the diagnosis and management of patients with SLE, a tool for measurement of clinical activity for pharmaceutical development and basic research of the disease and a reference work for hospital libraries.
- Provides the very latest overview of the pathogenesis of SLE
- Distills current understanding of the cellular, molecular, genetic and environmental factors that instigate and drive the disease
- Includes comprehensive coverage of clinical features, including fatigue, organ system manifestations, overlap syndromes, infections, and more
- Conveys the very latest understanding of mechanisms of tissue damage, including immune complexes, antibodies, and other mechanisms that lead to organ damage
- Discusses the latest treatment options on disease modifying or disease controlling agents
- Provides 'one stop' coverage of all the latest scientific and clinical developments in SLE
researchers in basic, applied, and clinical immunology
- Dedication
- List of Contributors
- Introduction
- Part I. Epidemiology and Diagnosis
- Chapter 1. History of Systemic Lupus Erythematosus
- Chapter 2. The Patient
- Improve the 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
- Chapter 8. Overview of the Pathogenesis of Systemic Lupus Erythematosus
- Part III. Mechanisms of Tissue Damage
- Chapter 33. Mechanisms of Renal Damage in Systemic Lupus Erythematosus
- Introduction
- dsDNA Is Not the Only Autoantigen in LN
- Anti-dsDNA Abs May Not Be the Abs That Initiate LN
- Breaking Tolerance to DNA, Nucleosome, and Other Nuclear Ags Is Not Required for the Pathogenesis of LN
- IC Deposition with Complement Activation Is Not Sufficient for LN to Progress from aGN to cGN and End Stage Renal Disease
- Multiple Cells and Cytokines Are Involved in the Pathogenesis of LN
- Kidney Disease in Lupus Is Not Always “Lupus Nephritis”
- Regeneration and Fibrosis Are Keys to Recovery from LN
- Concluding Remarks
- Chapter 34. Mechanisms of Vascular Damage in Systemic Lupus Erythematosus
- Summary
- Epidemiology of Vascular Damage in Systemic Lupus Erythematosus
- Risk of Vascular Damage: Traditional versus Nontraditional Factors
- Role of Cytokines in Vascular Damage in SLE
- Autoantibodies and Immune Complexes
- Cellular Mediators
- Oxidized Lipoproteins
- Modulation of CV Risk in SLE
- Chapter 35. The Mechanism of Skin Damage
- Introduction
- Clinical Aspects
- Pathogenesis of Skin Damage
- Chapter 36. Pathogenesis of Tissue Injury in the Brain in Patients with Systemic Lupus Erythematosus
- Introduction
- Focal Brain Injury Depends on Cerebrovascular State and an Activated Adaptive Immune Response
- Diffuse Neurological Disease
- Animal Models Abet Mechanism Investigation
- Autoantibody Toxicity in Clinical SLE
- Blood–Brain Barrier
- Transport of Maternal IgG to Fetal Brain
- Cytokines and Other Soluble Toxic Molecules
- Conclusions
- Chapter 33. Mechanisms of Renal Damage in Systemic Lupus Erythematosus
- Part IV. Clinical Aspects of the Disease
- Chapter 37. Constitutional Symptoms and Fatigue in Systemic Lupus Erythematosus
- Introduction
- Fatigue
- Fever
- Lymphadenopathy
- Splenomegaly
- Weight Loss
- Conclusions
- Chapter 38. The Musculoskeletal System in Systemic Lupus Erythematosus
- Summary
- Arthritis
- Tendon Rupture
- Myositis
- Osteonecrosis
- Osteoporosis
- Chapter 39. Cutaneous Lupus Erythematosus
- Epidemiology
- Classification Criteria for SLE
- Photosensitivity
- Cutaneous Manifestations
- Scores in Cutaneous Lupus Erythematosus
- Subtypes of Cutaneous Lupus Erythematosus
- Conclusion
- Chapter 40. The Clinical Evaluation of Kidney Disease in Systemic Lupus Erythematosus
- Introduction
- The Scope of Lupus Nephritis
- The Diagnosis of Lupus Nephritis
- The Kidney Biopsy
- Antiphospholipid Syndrome and the Kidney
- Pregnancy and Lupus Nephritis
- Childhood Lupus Nephritis
- Conclusion
- Chapter 41. The Pathology of Lupus Nephritis
- Introduction
- Introduction to Nephropathology
- Introduction to the Nephropathology of SLE
- Renal Biopsy and SLE
- The Lesions of Lupus Nephritis
- Classification of Lupus Nephritis
- Selected Topics in Classification
- Treatment and Transformation
- Selected Clincopathologic Topics
- Chapter 42. Cardiovascular Disease in Systemic Lupus Erythematosus
- Introduction
- Traditional Risk Factors for CVD in Lupus
- Novel Mechanisms and Areas of Investigation
- Therapeutic Paradigms for Atherosclerosis
- Other Cardiac Manifestations of Lupus
- Conclusions and Future Directions
- Chapter 43. The Lung in Systemic Lupus Erythematosus
- Introduction
- Prevalence of Lung Involvement in SLE
- Pulmonary Infection
- Nonpulmonary Involvement as a Cause of Respiratory Symptoms
- Pleural Disease
- Parenchymal Disease
- Shrinking Lung Syndrome
- Pulmonary Vascular Disease
- Acute Reversible Hypoxia Syndrome
- Airway Disease
- Clinicians Should Screen For Lung Disease In SLE
- Summary
- Chapter 44. Gastrointestinal, Hepatic, and Pancreatic Disorders in Systemic Lupus Erythematosus
- Introduction
- The Gastrointestinal Tract in SLE
- The Liver in SLE
- Biliary Tract Disease in SLE
- The Pancreas in SLE
- Acute Abdominal Pain in SLE
- Conclusions
- Chapter 45. Systemic Lupus Erythematosus and Infections
- Introduction
- Epidemiology of SLE Infections
- Immunologic Pathogenesis of Infections in Systemic Lupus Erythematosus
- Treatment-Associated Immunosuppression and Infection Risk
- Type of Infections
- Preventative Strategies
- Chapter 46. Malignancies in Systemic Lupus Erythematosus
- Summary
- Introduction
- Hematologic Cancers
- Lung Cancers
- Cervical Cancer
- Breast, Ovarian, and Endometrial Cancers
- Conclusions
- Chapter 47. The Nervous System in Systemic Lupus Erythematosus
- Summary
- Introduction
- Classification and Clinical Manifestations
- Etiology and Pathogenesis of NPSLE
- Cognitive Dysfunction in SLE
- Diagnostic Approach for NPSLE
- Treatment of NP Events in SLE Patients
- Autoimmune Inflammation-Mediated Injury
- Vascular-Mediated Injury
- Cognitive Impairment
- Prognosis
- Conclusion
- Chapter 48. Overlap Syndromes
- Summary
- Introduction
- Clinical and Laboratory Manifestations of Overlap Syndromes
- Immunology of Overlap Syndromes
- Genetics
- Animal Models
- Treatment
- Chapter 49. Systemic Lupus Erythematosus and the Eye
- Introduction
- The Role of Ophthalmic Features in the Criteria for Classification and Disease Activity
- Clinical Presentation
- Investigations
- Treatment
- Conclusion
- Chapter 50. Pregnancy and Fertility in Systemic Lupus Erythematosus
- Systemic Lupus Erythematosus—A Manual
- Fertility and SLE
- Pregnancy in SLE Patients
- Management of SLE during Pregnancy
- Conclusions
- Chapter 51. Neonatal Lupus: Clinical Spectrum, Biomarkers, Pathogenesis, and Approach to Treatment
- Introduction
- Risk of Cardiac NL and Population Prevalence
- Transient Clinical Manifestations of NL: Cutaneous, Hepatic, Hematologic, and Neurologic
- Immutable Manifestations of NL: Cardiac
- Factors Contributing to Mortality
- Seeking Biomarkers: The Candidate Autoantibodies
- Linking Antibody to Tissue Damage and Fibrosis: Accounting for Antigen Target Accessibility
- Guidelines for Monitoring Anti-SSA/Ro-Exposed Pregnancies and Approach to Cardiac NL
- Translating Pathogenesis to Prevention
- Chapter 52. Incomplete Lupus
- Summary
- Definition
- Incomplete Lupus versus Undifferentiated Connective Tissue Disease (UCTD)
- Epidemiology
- Transition from Incomplete Lupus Erythematosus (ILE) to SLE
- Treatment
- Chapter 53. Childhood-Onset Systemic Lupus Erythematosus
- Summary
- Epidemiology
- Clinical Manifestations
- Familial SLE
- Morbidity and Mortality
- Therapeutic Considerations in Children
- Chapter 54. Drug-Induced Lupus
- Summary
- Introduction
- Epidemiology
- Diagnosis
- Treatment of Drug-Induced Lupus
- Conclusion
- Chapter 55. Vasculitis in Lupus
- Summary
- Prevalence and Associated Features of Vasculitis in Lupus
- Cutaneous Vasculitis
- Lupus Mesenteric Vasculitis
- Large Vessel Vasculitis
- Other Forms of Vasculitis
- Chapter 37. Constitutional Symptoms and Fatigue in Systemic Lupus Erythematosus
- Part V. Antiphospholipid Syndrome
- Chapter 56. Pathogenesis of Antiphospholipid Syndrome
- Introduction
- Pathogenesis of aPL
- Interaction of aPL with Cells
- Conclusion
- Chapter 57. Antibodies and Diagnostic Tests in Antiphospholipid Syndrome
- Summary
- Antiphospholipid Syndrome as an Autoantibody-Mediated Disease
- Classification Laboratory Assays
- Nonclassification Laboratory Assays
- Other Autoantibodies in Antiphospholipid Syndrome
- Chapter 58. Clinical Manifestations
- Summary
- Introduction
- Vascular Thrombosis
- Pregnancy Morbidity
- Catastrophic APS
- Features Associated with aPL
- Chapter 56. Pathogenesis of Antiphospholipid Syndrome
- Part VI. Treatment of the Disease
- Chapter 59. Nonsteroidal Anti-inflammatory Drugs in Systemic Lupus Erythematosus
- Introduction
- Inhibitory Role of NSAIDs
- Effects on the Kidneys
- Gastrointestinal Side Effects
- Increased Cardiovascular Risk: What Is the Verdict?
- Central Nervous System (Aseptic Meningitis) Side Effects
- Effects on Reproduction
- Conclusion
- Chapter 60. Value of Antimalarial Drugs in the Treatment of Lupus
- Introduction
- Pharmacokinetics and Pharmacodynamics of Antimalarials
- Mechanisms of Action
- The Beneficial Effects of Antimalarials in SLE
- Practical Aspects Related to the Use of Antimalarials
- Screening for Glucose-6-Phosphate Dehydrogenase Deficiency
- Nonophthalmologic Adverse Effects of Antimalarial Agents
- Ophthalmologic Adverse Effects of Antimalarial Agents
- Use of Antimalarials in Pregnancy and Lactation
- Chapter 61. Systemic Glucocorticoids
- Introduction
- Nomenclature
- Rationale and Mechanism of Action of Glucocorticoids in SLE
- Forms and Mode of Administration of Systemic Corticosteroids
- Approach to the Use of Glucocorticoids Based on Organ System Involvement
- Tapering and Withdrawal of Glucocorticoids
- Side Effects of Corticosteroids
- Future Direction
- Chapter 62. Cytotoxic-Immunosuppressive Drug Treatment
- Summary
- Introduction
- Alkylating Agents
- Nucleotide Synthesis Inhibitors
- Calcineurin Inhibitors
- General Issues in Lupus Patients on Cytotoxic/Immunosuppressive Drug Treatment
- Chapter 63. Treatment of Antiphospholipid Syndrome
- Introduction
- Primary Thromboprophylaxis
- Prevention of Recurrent Thrombosis
- Alternative Therapies for Refractory and Difficult Cases
- Other Therapies
- Pregnancy
- Recurrent Early Miscarriage
- Fetal Death
- Management of Pregnancy in Patients with APS and Previous Thrombosis
- Management of Refractory Obstetric APS
- Postpartum Period
- Chapter 64. New Treatments for Systemic Lupus Erythematosus
- Summary
- Cytokines
- Complement
- Co-Stimulatory Pathways
- Cell Surface Molecules
- Conclusion
- Chapter 65. Management Lessons from Clinical Trials of Kidney Disease in Systemic Lupus Erythematosus
- Summary
- Kidney Disease in Systemic Lupus Erythematosus
- Patient Selection in Clinical Trials
- End points for Clinical Trials
- Matching Clinical Trial Expectations to the Experimental Therapeutic
- Conclusion
- Chapter 66. Repositioning Drugs for Systemic Lupus Erythematosus
- Why Try to Repurpose Drugs for SLE Patients?
- LRxL-STATTM: Repositioning Treatments for SLE Patients
- Identification of Top Priority LRxL-STATTM Candidates
- Summary
- Chapter 59. Nonsteroidal Anti-inflammatory Drugs in Systemic Lupus Erythematosus
- Appendix
- Index
- Edition: 1
- Published: December 23, 2015
- Language: English
GT
George C. Tsokos
George C. Tsokos, MD, is a Professor of Medicine at Harvard Medical School and Chief of Rheumatology and Clinical Immunology at Beth Israel Deaconess Medical Center. Dr Tsokos has served as President of the Clinical Immunology Society, on the boards of directors for the American College of Rheumatology and the Lupus Foundation of America, member/chair of multiple federal study sections, and editor/member of the editorial boards for top scientific journals. He has received several awards, including a MERIT from NIH, the Lee C. Howley Sr. Prize, the Evelyn V. Hess, the Distinguished Basic Investigator Award from the American College of Rheumatology, the Lupus Insight Prize from the Lupus Research Alliance, and the Carol Nachman Prize for Rheumatology. He is a Master of the American College of Physicians and the American College of Rheumatology, a member of American Association of Physicians and Fellow of AAAS.
Affiliations and expertise
Professor of Medicine, Harvard Medical School and Chief of Rheumatology and Clinical Immunology, Beth Israel Deaconess Medical Center, USARead Systemic Lupus Erythematosus on ScienceDirect