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Autoimmune diseases (Rose)
The autoimmune diseases / edited by Noel Richard Rose, Ian R. MacKay.
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Title:[Autoimmune diseases (Rose)]
The autoimmune diseases / edited by Noel Richard Rose, Ian R. MacKay.
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Other Contributors/Collections:Rose, Noel R., editor.
Mackay, Ian R., editor.
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Published/Created:Amsterdam : Elsevier/Academic Press, 2014.
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Holdings
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Location:WOODWARD LIBRARY stacksWhere is this?
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Call Number: WD305 .A9377 2014
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Number of Items:1
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Status:Available
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Location:WOODWARD LIBRARY stacksWhere is this?
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Library of Congress Subjects:Autoimmune diseases.
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Medical Subjects: Autoimmune Diseases.
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Edition:Fifth edition.
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Description:xxxiii, 1, 267 pages : illustrations (some colored) ; 29 cm
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Summary:This edition of 'Autoimmune Diseases' incorporates new material and combines common themes underlying inductive and effector mechanisms and therapies that relate generally to the autoimmune disorders. It discusses the biological basis of disease at genetic, molecular, cellular, and epidemiologic levels.
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Notes:Previous edition: 2006.
Includes bibliographical references and index.
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ISBN:9780123849298 (hbk.)
0123849292 (hbk.)
9780123849304 (PDF ebook)
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Contents:Machine generated contents note: pt. 1 Immunologic Basis of Autoimmunity
1. Autoimmune Disease: The Consequence of Disturbed Homeostasis / Ian R. Mackay
Evolution of the Autoimmune Response
Phylogenetic Perspective
Innate Immune System
Adaptive Immune System
Self and Non-Self, and the Nature of Autoantigens
Autoimmunity and Autoimmune Disease
Common Threads
"Proper Study..."
Towards the Future
Last Word
References
2. Autoimmunity: A History of the Early Struggle for Recognition / Arthur M. Silverstein
Search for Autoantibodies
Horror Autotoxicus
Nature of Ehrlich's "Contrivances"
Challenges to the Thesis
Lens Autoantibodies
Paroxysmal Cold Hemoglobinuria
Sympathetic Ophthalmia
Wassermann Antibody
Shift to Immunochemistry
Return of Immunobiology
Concluding Remarks
References
3. General Features of Autoimmune Disease / Betty Diamond
Innate Immune Activation
Cells of the Adaptive Immune System
Defining Autoimmune Disease
Prevalence of Autoimmunity
Genetics of Autoimmunity
Association of Single Gene Defects with Autoimmunity
Genome-wide Association Studies (GWAS) Identify Multiple Gene Loci that are Associated with Autoimmunity
Hormones and Autoimmunity
Autoimmunity and Central Tolerance
Autoimmunity and Peripheral Tolerance
Triggers of Autommunity
Activation of the Immune System
Role of Antigen as a Driver of Autoimmunity
Defective Downregulation of an Immune Response
Regulatory Lymphocytes
Role of the Gut Microbiota in Autoimmunity
Mechanisms of Tissue Damage
Flares and Remissions During Disease
Therapeutic Advances
Goals for the Future
Concluding Remarks
Acknowledgments
References
4. Concept of Autoinflammatory Diseases / Anna Simon
Historical Perspective
Definition
Spectrum from Autoimmune to Autoinflammatory Disease
Mechanisms in Autoinflammation
Classical Hereditary Autoinflammatory Disorders
Common Phenotype
Cryopyrin-Associated Periodic Syndrome
Familial Mediterranean Fever
TNF Receptor-Associated Periodic Syndrome
HIDS (also Known as Mevalonate Kinase Deficiency)
Polygenic or Acquired Autoinflammatory Disorders
Autoinflammatory Mechanisms of Disease in Common Disorders
Type 2 Diabetes Mellitus
Atherosclerosis
Newest Developments: Rare Hereditary Disorders with Autoinflammatory Aspects
Proteasome Defects
PLCγ2 Deficiency
Heme-Oxidized IRP2 Ubiquitin Ligase
Conclusion
References
pt. 2 Immune Cells and Immune Responses
5. Innate and Adaptive Systems of Immunity / Peter J. Delves
Introduction
Innate and Adaptive Responses
Innate Responses
Cellular Components
Soluble Mediators
Adaptive Immune Responses
T Cell Development
Functional Activities of T Cells
B Cell Development and Functions
Antibodies
Secondary Lymphoid Tissues
Resolution of the Immune Response
References
6. T Cells and their Subsets in Autoimmunity / Vijay K. Kuchroo
Introduction
TH1 Cells
TH17 Cells
Discovery and Differentiation
Function
Reciprocal Relationship with Tregs
Role of IL-23 in the Generation of Th17 Cells
Th17 Pathogenicity and Plasticity
Th17 Regulation in the Intestine
Regulatory CD4+ T Cells
Tr1 Cells
TFH Cells
Th2 Cells
Th9 Cells
Concluding Remarks
References
7. Immunological Tolerance
-T Cells / Pamela S. Ohashi
Early Studies Supporting the Induction of Tolerance
Thymic Tolerance
Brief Overview of Thymocyte Development
Mechanisms of Thymic Tolerance
Expression of Tissue-Restricted Antigens in the Thymus
Peripheral Tolerance
Impact of Dendritic Cells
Mechanisms of Peripheral Tolerance
Expression of Tissue-Specific Antigens by Lymph Node Stromal Cells
Concluding Remarks
Acknowledgments
References
8. Role of Invariant Natural Killer T Cells in Autoimmune Diseases / Mitchell Kronenberg
Curious Case of iNKT Cells
Many Names of NKT Cells
Many Faces of iNKT Cells
Many Effector Functions of iNKT Cells
Many Kinds of iNKT Cells
Technical Problems and the Species Divide
Janus-Like Character of iNKT Cells in Autoimmunity
Too Much of a Good Thing: Detrimental Roles of iNKT Cells
Missed so Sadly: Beneficial Roles of iNKT Cells
Good or Bad Performers?
Far End of the Question?
Conclusion
Acknowledgments
Abbreviations
References
9. B Cell Development: How to Become One of the Chosen Ones / Fritz Melchers
Introduction
-What has to be Generated in B Cell Development to Make it to Maturity?
Follicular B Cells
Intraepithelial B Cells
Two Types of Memory B Cells
B Lymphopoiesis Before Ig Repertoire Generation
-Development of Progenitor and Precursor Cells
Development in Waves During Ontogeny, and in Niches Throughout Life
Cellular Environments of the First Phase of Early, Antigen-Independent B Cell Development
Early Commitments to Antigen-Independent B Cell Development
Second, Eventually Autoantigen-Sensitive, Phase of B Cell Development to slgM+ Immature B Cells
First Checkpoint for the Emerging B Cell Repertoire
-Probing the Fitness for a Good BCR
Expression of IgL Chains
Second Checkpoint: Sites and Mechanisms of Selection of Newly Generated slgM+ B Cells
Future Approaches to Understanding Central B Cell Tolerance
Acknowledgments
References
10. B Cell Activation and B Cell Tolerance / Paul A. Blair
B Cell Activation
Antigen-Triggered Activation
Secondary Signals for B Cell Activation
Immediate Consequences of B Cell Activation
B Cell Activation Requires Interaction with Helper T cells
Cell Surface Molecules Involved in B Cell-T Cell Interactions
Cytokines Involved in B Cell-T Cell Interactions
Activation and Maturation of B Cells Occurs in Lymphoid Organs
Where Do B Cells become Antigen Activated?
Antigen Activation of B Cells Leads to the Selection of High Affinity Class-Switched Antibody
Germinal Center
T Cell-Independent Antibody Responses
B Cell Tolerance: A Traditional and New Concept
B Cell Tolerance is Acquired by at Least Three Different Processes
Receptor Editing and Clonal Deletion
Defective Receptor Editing Can Promote Autoimmunity
Anergy
Characteristics of Anergic B Cells
Survival Factors and Tonic Signals Modulate B Cell Tolerance
Tonic Signaling in B Cell Development
Tonic Signaling and Autoimmunity
BAFF and Autoimmunity
Regulatory T cells
Antibody-Independent Activity of B cells in Tolerance
Cytokine Production by B Cells
Regulatory B Cells
Future Directions
References
pt. 3 Non-Antigen-Specific Recognition
11. Role of Macrophages in Autoimmunity / Annette Pluddemann
Introduction
Origin and Distribution of Monocytes and Macrophages
Recognition, Sensing, and Responses
Phagocytosis, Antigen Presentation, and Secretion
Activation and Downregulation: Interactions with T and B Lymphocytes
Role of Macrophages in Adaptive Immunity and Tolerance
Role of Macrophages in Autoimmune Models and Diseases
Generation of Autoantigens
Modulation of Macrophage Activation
Conclusions and Questions
Acknowledgments
References
12. Dendritic Cells in Autoimmune Disease / Meredith O'Keeffe
Antigen Processing by Dendritic Cells
Pattern Recognition Receptors
Dendritic Cell Activation
Dendritic Cell Subsets
Mouse Dendritic Cells
Dendritic Cells in the Mouse Thymus
Dendritic Cell Subsets and Tolerance
Human Dendritic Cell Subsets in Steady State
Dendritic Cell Subsets in Human Skin: Epidermal Langerhans Cells and dermal Dendritic Cells
Dendritic Cells and Autoimmune Disease
Systemic Lupus Erythematosus
IBD
-Crohn's Disease and Ulcerative Colitis
Dendritic Cell Immunotherapy as a Treatment for Autoimmune Diseases
Targeting of Dendritic Cells in Autoimmune Disease
Conclusions and Future Prospects
References
13. Natural Killer Cells / Hans-Gustaf Ljunggren
Introduction to NK Cells
NK Cell Development and Differentiation
Phenotype and Tissue Localization of NK Cells
Functional Responses by NK Cells
NK Cell Receptor Signaling and Effector Functions
NK Cell Contact and Adhesion to Target Cells
NK Cell Lytic Granule Polarization and Maturation
NK Cell Cytolytic Granule Exocytosis
NK Cell Chemokine and Cytokine Production
NK Cells and Human Autoimmunity
Defective Control of other Immune Cells Links NK Cells to Autoimmune Diseases
Genetic Association Studies Revealing Links between NK Cells and Autoimmune Diseases
Conclusions
References
14. Granulocytes: Neutrophils, Basophils, Eosinophils / Manuel Ramos-Casals
Neutrophils
Basic Biology and Role in Immunity
Neutrophil Extracellular Traps and NETosis: A Novel Form of Cell Death
Pathogenic Role of Neutrophils in Autoimmune Diseases
Basophils
Basic Biology and Role in Immunity
Basophils in Autoimmune Diseases
Eosinophils
Basic Biology and Role in Immunity
Eosinophils in Churg-Strauss Syndrome
Conclusions and Therapeutic Implications
References
15. Roles and Contributions of the Complement System in the Pathophysiology of Autoimmune Diseases / Robert B. Sim
Complement System and Complement Activation Pathways
Classical Pathway
Lectin Pathway
Alternative Pathway
Membrane Attack Complex
Contents note continued: Control of Complement Activation
Fluid Phase Regulators
Membrane-Bound Regulators
Biological Effects of Complement Activation
Complement Involvement in the Pathophysiology of Diverse Autoimmune Diseases
References
16. Cytokines, their Receptors and Signals / Joost J. Oppenheim
Historical Perspective
Cytokines and Immunity
Cytokine Receptor Subsets
Common γc Chain Subset
βc Utilizing Subset
gp130 Utilizing Subset (IL-6 Family)
Cytokines Sharing either a p35 or p40 Ligand Chain
Th17 Cytokines and Receptors
Class II Cytokine Receptor Family
Type I Interferons α and β
Type II Interferon Gamma
Type III Interferon Lambda
Non-Interferon Members
TNF Receptor Family
IL-1/TLR Family of Receptors
Immunosuppressive Cytokines/Growth Factors
Chemokines
Alarmins
Conclusions
Acknowledgments
References
pt. 4 Initiation of Autoimmunity
17. Cellular Injury and Apoptosis / Philip L. Cohen
Apoptosis
History of Apoptosis
Molecular Pathways of Apoptosis
Apoptotic Cell Morphology
Apoptosis in Autoimmunity
Defective Apoptosis
Excessive Apoptosis and Apoptotic Cells as Sources of Autoantigen
Apotopes
NETosis
Necrosis
Necroptosis
Parthanatos {Par[poly(ADP-ribosyl)ation] and thanatos (death)}
Clearance of Dead Cells
Find-me Signals
Eat-me Signals and their Receptors
Receptors for Necrotic Cells
Anti-Inflammatory Effects of Apoptotic Cells
Immuno-Stimulatory Effects of Necrotic Cells
Glimpse into the Future
References
18. Autophagy in Autoimmunity / Christian Munz
Autophagy Pathways
Autophagy in Innate Immunity
Autophagy in Lymphocyte Development and Activation
Antigen Presentation for CD4+ and CD8+ T Cell Recognition
Autophagy in Tolerance and Autoimmunity
Future Prospects
References
19. Infectious Triggers of T Cell Autoimmunity / Stephen D. Miller
Introduction
Role of Infections in Priming of Autoreactive Immune Responses
Potential Mechanisms of Infection Triggering Autoimmunity
Molecular Mimicry
Bystander Activation of Autoreactive Cells and Epitope Spreading
Emerging Mechanisms of Infection-Induced Autoimmune Disease
Reciprocal Relationships of Pathogen-Derived Mechanisms of Autoimmunity
How do these Mechanisms Lead to Autoimmune Disease?
Autoimmunity Can Occur at a Site Distal to the Initiating Infection
Conclusions
Acknowledgments
References
20. Autoimmune Diseases: The Role for Vaccines / Paul-Henri Lambert
Introduction
Theoretical Concerns for Autoimmune Diseases in the Context of Vaccination
Crossfire and Coincidence
Challenges using Animal Models
One Size does "not" Fit All
Induced Autoimmune Disease in Animals
Spontaneous Autoimmune Disease in Animals
"Of Mice and Men"
-The Correct Application of Human Epidemiology and Translation of Human Immunology to Rodent Immunology
Practical Approach to Vaccination in Patients with Autoimmune Disease
Reality Facing Clinicians Currently
Certainty about Vaccines, Uncertainty about Compatibility of Administration in Certain Settings
Search and You Will Find
Conclusion
References
21. Non-infectious Environmental Agents and Autoimmunity / Frederick W. Miller
Introduction
Evidence Supporting the Role of Environmental Agents in Autoimmune Disease
Identifying and Defining Environmentally Associated Autoimmune Diseases
Non-Infectious Agents Associated with Autoimmune Diseases
Drugs
Occupational Exposures
Others
Possible Mechanisms by Which Environmental Agents May Induce Autoimmune Diseases
Overview and Future Directions
References
22. Adhesion Molecules and Chemoattractants in Autoimmunity / Ulrich H. von Andrian
Microvascular Determinants of T Cell Recruitment
Adhesion Molecules
Chemoattractants and their Receptors
Multistep Adhesion Cascades
Organized Lymphoid Tissues: Venues for Naive T Cell Homing and Dendritic Cell Interactions
Effector T Cell Migration
Homing to Non-Lymphoid Tissues
Some Clinical Applications
Conclusions and Future Directions
Acknowledgments
References
pt. 5 Facilitation of Autoimmunity
23. Effector Mechanisms in Autoimmunity / Martin Aringer
Introduction
Autoantibodies
Direct Antibody-Mediated Disease
Immune Complex Disease
Complement Cascades
Macrophages
Neutrophils
Mast Cells
Natural Killer Cells and Cytotoxic T Cells
Effector T Helper Cell-Mediated Autoimmune Disease
Effector Cytokines and their Targets
Conclusions
References
24. Sexual Dimorphism in the Immune System / Judith M. Greer
Introduction
Overview of Sexual Dimorphism
Sexual Dimorphism in the Immune System
Effects of Hormones on the Immune System
Estrogens
Progesterone
Androgens
Role of the Sex Chromosomes in Immunity
X Chromosome
Y Chromosome
Environmental Effects on Sex Differences in Immunity
Consequences for Autoimmunity of Sexual Dimorphism in the Immune System
Concluding Remarks
References
25. Microbiome and Autoimmunity / Alicia Perez-Arroyo
Introduction
Intestinal Microbiome
Intestinal Microbiome Composition and Genotyping Techniques
Microbiome Changes Over a Lifetime
Intestinal Microbiome Depends on the Environment
Germ-Free (GF) Animals
Effect of a GF Environment on Experimental Diseases
Non-Obese Diabetic Mouse
Experimental Allergic Encephalomyelitis
Experimental Arthritis
Murine Lupus
Microbiome Composition and Autoimmune Diseases
Type 1 Diabetes
Rheumatoid Arthritis
Effect of Probiotics on Autoimmune Diseases
Probiotic Mixtures
Specific Probiotics
Role of Toll-like Receptor Stimulation
Relationship Between the Intestinal Microbiome and the Hygiene Hypothesis
Brief Overview of the Hygiene Hypothesis
Clean Environment Promotes the Onset of Autoimmune Diabetes
Autoimmune Diseases Can be Prevented by Infections With a Pathogen
Synthesis and Conclusions
Strength of the Protective Effect of Pathogens
Ambiguous Effect on Autoimmune Disease of the GF or Axenic Status
Delicate Interpretation of the Reduction in the Diversity of the Intestinal Microbiome
Perspectives
Acknowledgments
References
26. Genetic Predisposition, Humans / Alan G. Baxter
Introduction
Diseases of Interest
Type 1 Diabetes
Multiple Sclerosis
Systemic Lupus Erythematosus
Human Leukocyte Antigen (HLA) Complex and other Candidate genes
Association of Type 1 Diabetes with HLA and other Candidate Genes
Association of Multiple Sclerosis with HLA and other Candidate Genes
Association of Lupus with HLA and other Candidate Genes
Mechanisms of Complement and Fc Associations with Autoimmunity
Mechanisms of HLA Association with Autoimmunity
Gene Linkage Studies of Autoimmunity
Linkage Studies of Type 1 Diabetes
Linkage Studies in Multiple Sclerosis
Linkage Studies in Lupus
Genome-Wide Association Studies of Autoimmunity
Genome-Wide Association Studies of Type 1 Diabetes
Genome-Wide Association Studies of Multiple Sclerosis
Genome-Wide Association Studies of Systemic Lupus Erythematosus
From Location to Molecular Mechanisms
Concluding Comments
Acknowledgments
References
27. Genetic Predisposition to Autoimmune Diseases Conferred by the Major Histocompatibility Complex: Utility of Animal Models / Chella S. David
Major Histocompatibility Complex
MHC and Autoimmunity
Mystery of HLA-B27 and Spondyloarthropathies
HLA Class II Association with Autoimmune Diseases
Predisposition
Onset
Environmental Factors
Infectious Agent
Porphyromonas Gingivalis and Rheumatoid Arthritis
Smoking and Autoimmunity
Vitamin D in Autoimmune Diseases
Post-Translational Modifications in Autoimmunity
Deimination
Deamidation
Humanized Animal Models of Autoimmunity
Collagen-Induced Arthritis
Non-RA-Associated HLA Alleles Can Predispose to Autoimmunity
HLA-DR Transgenic Mice with EAE as an Animal Model of MS
Role of DQ Molecules in Predisposition to MS
Animal Model of Celiac Disease
Animal Model for Type 1 Diabetes
HLA Class II Molecules Regulate Infection Through Modulation of Cytokine Networks
Concluding Remarks
References
28. Epigenetics and Autoimmune Diseases / Moncef Zouali
Epigenetic Modifications
DNA Methylation
Histone Post-Translational Modifications
Acetylation and Deacetylation
Histone Methylation
Arginine Methylation
Ubiquitination
MicroRNAs
Epigenetic Stability
Epigenetics of Immune Tolerance to Self
Epigenetic Regulators of Tolerant T Cells
Role of CpG DNA Methylation in Treg Development and Function
Impacts of Histone Acetylation on Development and Function of Tregs
Epigenetic Modulation of Treg Stability
Systemic Lupus Erythematosus
DNA Methylation
DNA Methylation Control by miRNA
Histone Acetylation
Environmental Epigenetics in SLE
Epigenetic Disruption of B Cell Tolerance in SLE
Rheumatoid Arthritis
Acetylation Marks
Genomic DNA Hypomethylation and the Activated Phenotype of RASFs
miRNA and the Destructive Potential of RASFs
Aberrant SUMOylation
Systemic Sclerosis
Sjogren's Syndrome
Antineutrophil Cytoplasmic Autoantibodies-Associated Vasculitis
Contents note continued: Type 1 Diabetes
DNA Methylation Profiling
Chromatin Remodeling and Histone Acetylation
Histone Deacetylase Inhibitors in Preclinical Studies
Multiple Sclerosis
Generation of Neo-Epitopes
DNA Hypomethylation
Deregulation of Acetylation Homeostasis
Epigenetic Therapy
Targeting DNA Methylation
Histone Deacetylase Inhibitors
Epigenetic Generation of Tregs
Future Prospects
References
29. Autoimmunity in Primary Immunodeficiency Disorders / Arnold I. Levinson
Introduction
T Cell Developmental Defects
Severe Combined Immunodeficiency
Combined Immune Deficiencies
DiGeorge Syndrome
Wiskott-Aldrich Syndrome
Antibody Production Defects
X-Linked Agammaglobulinemia
Common Variable Immunodeficiency
Selective IgA Deficiency
Immunodeficiency with Hyper-IgM Syndrome
Innate Immune Defects
Chronic Granulomatous Disease
Early Complement Component Deficiency
Toll-Like Receptor 3 (TLR3) Polymorphism and Autoimmunity
Monogenic Defects Affecting Immune Homeostasis and/or Tolerance
Autoimmune Polyendocrinopathy, Candidiasis, Ectodermal Dystrophy
Immunodysregulation, Polyendocrinopathy, Enteropathy X-Linked
Autoimmune Lymphoproliferative Syndrome
Conclusion
Acknowledgment
References
pt. 6 Experimental Models of Autoimmunity
30. Animal Models: Systemic Autoimmune Diseases / George C. Tsokos
Introduction
Spontaneous Models of Systemic Autoimmunity
Genetically Manipulated Models of Systemic Autoimmunity
Lymphocyte Activation Molecules
Ubiquitination-Protein Ligases
Cytokines and their Receptors
Complement and Complement Receptor Proteins
Clearance of Dead Cells
Innate Immune Cell Signaling
Induced Models of Systemic Autoimmunity
Concluding Comments
References
31. Animal Models of Organ-Specific Autoimmune Disease / Matthias von Herrath
What Can Animal Models Teach us about Organ-Specific Autoimmunity?
Inciting Autoantigen
Antigen-specific Tolerization Strategies
Other Immune Therapies
Gene Function
Understanding the Complexity of Organ-Specific Autoimmunity
Animal Models
-Advantages and Disadvantages
Animal Models for Organ-Specific Autoimmune diseases
Spontaneous Models of Organ-Specific Autoimmunity
Genetically Engineered Animal Models for Organ-Specific Autoimmunity
Induced Animal Models for Organ-Specific Autoimmune Diseases
Protein/Peptide and Adjuvant
Cell Transfer or Depletion
Comparison of Organ-Specific Autoimmune Disease in Animal Models and Humans
Conclusions
References
pt. 7 Multisystem Autoimmune Diseases
32. Systemic Lupus Erythematosus / Robert G. Lahita
Introduction
Pathogenesis
Genetics
Epidemiology
Autoantibody
Clinical
Measurement of Clinical Activity
Musculoskeletal
Renal
Neuropsychiatric
Cardiac
Pulmonary
Hematology
Dermatology
Gastroenterological
ENT and Eye
Lupus Therapeutics
References
33. Systemic Sclerosis, Scleroderma / Daniel E. Furst
Introduction
Clinical, Pathologic, and Epidemiologic Features
Clinical Features
Pathologic Features
Epidemiologic Features
Autoimmune Features and Immunologic Markers in Disease
Potential Pathogenetic Antibodies
Diagnostic and Prognostic Antibodies
Genetic Features
Environmental Influences
Animal Models of SSc
UCD200 Chickens
Tsk1 and Tsk2 Mice
Scl-GvHD
TGF-β, CTGF, and bFGF
Bleomycin-Induced Fibrosis
Fra2-Transgenic Mice
TβRIIΔk Mice
Wnt-10b-Transgenic Mice
Pathogenic Mechanisms
Vasculopathy
Immunological Abnormalities
Fibrosis
Concluding Remarks and Future Prospects
References
34. Antiphospholipid Syndrome / Yehuda Shoenfeld
Introduction
Clinical Spectrum of Antiphospholipid Syndrome
Obstetric APS
Thrombotic APS
Neurological APS
Hematologic APS
Dermatologic APS
Cardiac APS
Pulmonary APS
Renal APS
Catastrophic Antiphospholipid Syndrome
Antiphospholipid Antibodies
b2GPI-Anti-b2GPI Complex in APS
Non-Criteria aPL Antibodies
aPL of the IGA Isotype
Low-level aPL
Mechanisms of aPL-Mediated Disease Expressions
Thrombotic Manifestations
Obstetric Manifestations
Neurologic Manifestations
Complement System in APS
Treatment of APS
Conclusions and Future Aspects
References
35. Sjogren's Syndrome / Haralampos M. Moutsopoulos
Introduction
Clinical Features
Local Manifestations (Salivary and Lachrymal Glands)
Systemic Manifestations (Beyond Salivary and Lachrymal Glands)
Overlapping Autoimmune Entities
Diagnosis and Differential Diagnosis
Autoimmune Features and Pathogenic Mechanisms
Immunopathology
Autoantibodies
Etiopathogenesis
Genetics
Epigenetics
Environmental Factors
Exocrine Gland Dysfunction
Apoptosis
Neurotransmission
Aquaporins
Structural Abnormalities
Therapy
Future Prospects
References
36. Rheumatoid Arthritis / Kurt Redlich
Introduction
Clinical, Pathologic, and Epidemiologic Features
Autoimmune Features
Genetic Features
In Vivo Models
Pathologic Effector Mechanisms
Autoantibodies as Potential Immunologic Markers
Concluding Remarks
-Future Prospects
Acknowledgment
References
37. Juvenile Idiopathic Arthritis / Alberto Martini
Epidemiology
Clinical Features
Systemic Arthritis
Rheumatoid Factor-Positive Polyarthritis
Enthesitis-Related Arthritis
Oligoarthritis
Rheumatoid Factor-Negative Polyarthritis
Psoriatic Arthritis
Undifferentiated Arthritis
Perspectives
Etiology and Pathogenesis
Systemic Juvenile Idiopathic Arthritis
Oligoarticular Juvenile Idiopathic Arthritis
Treatment
References
38. Spondyloarthritides / Joachim Sieper
Definition, Epidemiology, Clinical Manifestations, and Treatment
Reactive Arthritis
Arthritis with IBD
Psoriatic Arthritis
Role of HLA-B27 in the Pathogenesis of Spondyloarthritis
Arthritogenic Peptide Hypothesis
Misfolded HLA-B27 Hypothesis
Role of Non-MHC Genes in Spondyloarthritis
Bacterial Trigger and Autoimmunity in the Pathogenesis of the Spondyloarthritides
Cytokines in the Pathogenesis of Reactive Arthritis
Cytokines in the Pathogenesis of Ankylosing Spondylitis
What is the Immune Target in Ankylosing Spondylitis?
Inflammation and Bone Formation
Concluding Remarks
-Future Prospects
References
39. Autoimmune Myopathies / Antony Rosen
Defining Autoimmune Myopathies
Clinical and Pathological Descriptions of Different Phenotypes, including IMNM
Characteristic Pathology, but Significant Overlap between Phenotypes
Epidemiological Clues into Mechanism
Specific Autoantibodies are Strongly Associated with Phenotype, Making them Useful Probes of Disease Mechanism
Myositis-Specific Autoantibodies
HMG CoA Reductase Autoantibodies in Statin-Associated Immune-Mediated Necrotizing Myopathy
Mechanisms of Disease
Association of Malignancy with Myositis: Insights into Disease Initiation
Enhanced Expression of Myositis Autoantigens in Regenerating Muscle Cells to Focus Propagation on Muscle
Modification of Autoantigen Expression or Structure by Immune Effector Pathways to Generate a Self-Sustaining Phenotype
Therapeutic Insights
Concluding Remarks
References
pt. 8 Endocrine System
40. Thyroid Disease / Anthony P. Weetman
Autoimmune Thyroiditis
Historic Background
Clinical, Pathologic, and Epidemiologic Features
Autoimmune Features
Genetic Features
Environmental Influences
In Vivo Models
Pathologic Effector Mechanisms
Autoantibodies as Potential Immunological Markers
Treatment and Outcome
Concluding Remarks
-Future Prospects
Graves' Disease
Historic Background
Clinical, Pathologic, and Epidemiologic Features
Autoimmune Features
Genetic Features
Environmental Influences
In Vivo Models
Pathologic Effector Mechanisms
Autoantibodies as Potential Immunological Markers
Treatment and Outcome
Thyroid-Associated Ophthalmopathy and Dermopathy
Concluding Remarks
-Future Prospects
References
41. Autoimmune (Type 1) Diabetes / Ake Lernmark
Introduction
Clinical and Pathologic Features
Epidemiologic Features
Genetic Features
HLA Genetic Factors: The DR-DQ Alleles
Non-HLA Genetic Factors
Autoimmune Features
Pathologic Effector Mechanisms
Triggering Autoimmunity
APCs in Genetically Predisposed Subjects
In Vivo and In Vitro Models
Autoantibodies as Potential Immunologic Markers
Concluding Remarks
-Future Prospects
References
42. Adrenalitis / Renato Zanchetta
Introduction
Anatomy and Physiology of the Adrenals
Epidemiology of Addison's Disease and Autoimmune Adrenalitis
Autoimmune Addison's Disease (AAD)
Histopathology
Focal Lymphocytic Adrenalitis
Diffuse Lymphocytic Adrenalitis
Animal Models
Induced Immunity
Spontaneous Animal Models of AD
Immunologic Studies
Genetic Predisposition
Cellular Immunity
Humoral Immunity
Natural History of AAD
Diagnosis of AAD
Clinical Manifestations
Hormonal Tests
Imaging
Different Clinical Presentations of AAD
Association with other Autoimmune Disorders
Therapy
Contents note continued: General Information
Acknowledgments
References
43. Polyendocrine Syndromes / Eystein S. Husebye
Historical Background
Clinical, Pathologic and Epidemiologic Features
Autoimmune Features
Genetic Features
Environmental Features
Animal Models
AIRE-Deficient Mouse as a Model for APS-1
Spontaneous Animal Models
Thymectomy Animal Model
Pathogenic Mechanisms
Immunologic Markers in Diagnosis
Treatment and Outcome
Concluding Remarks
-Future Prospects
Acknowledgments
References
44. Autoimmune Gastritis and Pernicious Anemia / Paul A. Gleeson
Clinical, Pathologic, and Epidemiologic Features
Autoimmune Features
Autoantibodies
T Cell Immunity
Genetic Features
In Vivo and In Vitro Models
Pathologic Effector Mechanisms
Autoantibodies as Potential Immunologic Markers
Concluding Remarks
-Future Prospects
References
45. Autoimmune Hypophysitis / Angelika Gutenberg
Definition and Classification of Autoimmune Hypophysitis
Historical Background
Epidemiology and Body of Literature
Clinical Features
Pathological Features
Autoimmune Features
Genetic and Environmental Influences
Animal Models
Diagnosis
Treatment
Outcome
Hypophysitis Secondary to CTLA-4 Blockade
Concluding Remarks
-Future Perspectives
Acknowledgments
References
pt. 9 Blood Disorders
46. Autoimmune Hemolytic Anemia / Robert N. Barker
Historical Background
Classification of AIHA
Animal Models of AIHA
Mechanisms of RBC Destruction in AIHA
Cold Reactive Antibodies
Warm Reactive Antibodies
Pathogenicity of Warm Reactive IgG Antibodies
Additional Mechanisms of Hemolysis by Warm Antibodies
RBC Autoantigens
Clinical Signs of AIHA
Laboratory Diagnosis of AIHA
Treatment of AIHA
Etiology of AIHA and Predisposing Factors
Genetic Predisposition
Gender and Age
Infectious Agents
Drugs
Neoplasia
Immune Mechanisms Underlying Loss of Self Tolerance in Warm AIHA
B Cells and Tolerance
T Helper (Th) Cells and Tolerance
Concluding Remarks
References
47. Immune Thrombocytopenia / James B. Bussel
Clinical, Pathologic, and Epidemiologic Features
General Features and Definitions
Diagnosis
Epidemiology and Clinical Presentation in Children
Epidemiology and Clinical Presentation in Adults
Autoimmune Features
Autoimmune Markers in Primary ITP
Evans Syndrome
ITP Secondary to Systemic Lupus Erythematosus
ITP Secondary to Primary Immunodeficiencies
Genetics Features
Familial ITP
Genetic Markers of ITP
In Vivo Models
Pathologic Effector Mechanisms
Increased Platelet Destruction
Insufficient Platelet Production
Infection-related Thrombocytopenia
Autoantibodies as Potential Immunologic Markers
Concluding Remarks
-Future Prospects
References
48. Autoimmune Neutropenia / Parviz Lalezari
Historical Background
Clinical and Pathologic Features
Autoimmune Neutropenia of Infancy
Primary Autoimmune Neutropenia in Adolescents and Adults
Neutrophil-Specific Antigens in Primary Autoimmune Neutropenias
Secondary Autoimmune Neutropenias
Differential Diagnosis
Mechanisms of Cell Destruction
Laboratory Diagnosis
Treatment
Perspectives and Future Directions
References
49. Acquired Aplastic Anemia / Richard J. Jones
Historical Background
Genetic Features
Clinical, Pathologic, and Epidemiologic Features
Autoimmune Features and Pathogenic Mechanisms
Environmental Features
Animal Models
Therapy for Aplastic Anemia
Bone Marrow Transplantation (BMT)
BMT from Unrelated Donors
Immunosuppressive Therapy
High-Dose Cyclophosphamide without BMT
Aplastic Anemia and Clonality
Concluding Remarks
-Future Prospects
References
50. Monogenic Autoimmune Lymphoproliferative Syndromes / Michael Lenardo
Introduction
-Apoptosis and the Immune System
Clinical and Pathological Features
Autoimmune Lymphoproliferative Syndrome
Clinical Presentation
Laboratory Evaluation
Imaging Studies
Treatment
Prognosis
ALPS-Related Disorders
Caspase-8 and FADD Deficiencies
RAS-Associated Autoimmune Leukoproliferative Disorder
Genetic Features
Autoimmune Lymphoproliferative Syndrome (ALPS)
Germline FAS Mutations
Somatic FAS Mutations
Additional Genetic Etiologies
RAS-Associated Autoimmune Leukoproliferative Disorder
In Vivo and In Vitro Models of Disease
Pathogenic Effector Mechanisms
Conclusion
Acknowledgments
References
51. Autoimmune Clotting Dysfunction / Christoph Konigs
Introduction
Procoagulant Thrombotic Diseases
Autoimmune Inhibitors to ADAMTS13
Anticoagulant (Bleeding) Diseases
Autoimmune Antibody Inhibitors to Fibrinogen (Factor I) and Fibrin
Autoimmune Inhibitors to Prothrombin (Factor II) and Thrombin
Autoimmune Inhibitors to Factor V
Autoimmune Inhibitors to Factor VII
Autoimmune Inhibitors to Factor VIII
Autoimmune Inhibitors to Factor IX
Autoimmune Inhibitors to Factor X
Autoimmune Inhibitors to Factor XI
Autoimmune Inhibitors to Factor XII
Autoimmune Inhibitors to Factor XIII
Autoimmune Inhibitors to Von Willebrand Factor
Autoimmune Inhibitors to Further Proteins
Conclusions and Future Prospects
Acknowledgments
References
pt. 10 Central and Peripheral Nervous System
52. Multiple Sclerosis / David A. Hafler
Historical Background
Clinical Features
Imaging
Immunological Markers in Diagnosis
Pathology
Epidemiology of MS
Genetic Factors
Environmental Factors
Immune Pathogenesis
T Cell Pathogenesis
Immune Dysregulation
Autoantigens
Meningeal Ectopic B Cell Follicles
Treatment
Interferons
Glatiramer Acetate (Copaxone®)
Natalizumab (Tysabri®)
Mitoxantrone (Novantrone®)
Fingolimod (Gilenya®)
Teriflunomide (Aubagio®)
Dimethyl Fumarate, BG-12 (Tecfidera®)
Concluding Remarks
References
53. Peripheral Neuropathies / Kazim A. Sheikh
Introduction
Acute Neuropathies: The Guillain
Barre Syndrome
Historical Background
Epidemiology
Clinical Features and Subtypes of GBS
Autoimmune Features
Environmental Effects
Animal Models of Disease
Cellular Mechanisms
Cellular and Humoral Immune Elements are Synergistic
Genetic Aspects of GBS
Treatment and Outcomes
Chronic Neuropathies: Chronic Inflammatory Demyelinating Polyradiculoneuropathy
History
Epidemiology and Clinical Features
Autoimmune Features
Immunogenetic Features
Environmental Influences
Animal Models
Pathogenic Mechanisms
Treatment and Outcome
Concluding Remarks and Future Prospects
Acknowledgments
References
54. Myasthenia Gravis and Related Disorders / Angela Vincent
Introduction
Neuromuscular Junction
AChR, MuSK, and Lrp4
Neuromuscular Transmission
Myasthenia Gravis
Epidemiology
Etiology
General Aspects
Clinical Heterogeneity
Early-onset AChR Antibody Positive MG (AChRab+ MG)
Late-onset AChR Antibody Positive MG (AChRab+ MG)
Thymoma-Associated MG (Thymoma MG)
MuSK Antibody-Positive MG (MuSKab+ MG)
Neonatal MG
Antibodies in Myasthenia
Serological Testing
AChR Antibody Characteristics
MuSK and Other Antibodies
Pathogenic Mechanisms
Evidence for Pathogenicity of AChR and MuSK Antibodies
AChR Antibody-Positive MG
MuSK Antibody-Positive MG
Thymus and Cellular Immunity in MG
Role of T Lymphocytes in MG
Thymus and MG
Lambert
Eaton Myasthenic Syndrome
Epidemiology and Etiology
Clinical Features
Investigation and Treatment
Pathophysiology
Conclusions and Future Prospects
References
55. Ocular Disease / Robert B. Nussenblatt
Historical Background
Clinical Features
Pathologic Features
Epidemiologic Features
Autoimmune Features
Hormonal Influences
Genetic Factors
Animal Models
Pathogenic Mechanisms
Ocular Immune Responses
Tissue Destruction
Immunologic Markers
Treatment and Outcomes
Concluding Remarks and Future Prospects
References
56. Immune-Mediated Inner Ear Disease / Antonio Puccetti
Introduction
Clinical Features
IMIED Associated with Systemic Autoimmune Diseases
IMIED Associated with Primary Vasculitides
Evidence of Autoimmunity
Genetic Susceptibility
Animal Models
Treatment
Concluding Remarks and Future Perspectives
Acknowledgments
References
57. Encephalomyelopathies / Eric Lancaster
Introduction
Neurological Syndromes of Autoimmune Causation
Cerebral Syndromes
Ataxia
Spinal Myelitis
Stiff Person Syndrome
Systemic Immunopathic Disorders with Encephalitis and Myelitis
Systemic Lupus Erythematosus
Sarcoidosis
Sjogren's Syndrome
Behcet's Disease
Diseases with Autoantibodies to Cell-surface Channels, Receptors
Neuromyelitis Optica (NMO; Devic's disease)
Encephalitis with Antibodies to N-methyl-d-aspartate receptor (NMDAR)
Anti-AMPAR
Anti-GABA-B-R
Group 1 Metabotropic Glutamate Receptors (mGluR1, mGluR5)
Glycine Receptor (GlyR)
Voltage-Gated Potassium Channel Complex (VGKC)
LGI1
Caspr2
PCA-Tr
CNS Diseases with Autoantibodies to Intracellular Antigens
GAD65
Contents note continued: Amphiphysin I
Neuronal nuclear antigens (NNA)
Conclusions and Future Prospects
Acknowledgments
Abbreviations
References
58. Paraneoplastic Neurologic Syndromes / Jerome B. Posner
Introduction
Pathogenesis
Diagnosis
Antibodies
Nuclear/Nucleolar Antibodies
Cytoplasmic Antibodies
Synaptic/Cell Surface Antibodies
Ion Channel Antibodies
Treatment
Clinical Syndromes
Paraneoplastic Cerebellar Degeneration
Paraneoplastic Encephalomyelitis
Paraneoplastic Limbic Encephalitis
Brainstem Encephalitis
Myelitis
Subacute Sensory Neuronopathy
Autonomic Neuropathy
Vision Loss
Retinopathy
Optic Neuropathy
Stiff Person Syndrome
Lambert-Eaton Myasthenic Syndrome
References
pt. 11 Gastrointestinal System
59. Celiac Disease / Knut E.A. Lundin
Clinical, Pathologic, and Epidemiologic Features
Clinical Features and Associated Disorders
Pathology of the Intestinal Lesion
Epidemiology
Autoimmune Features
Autoantibodies
Autoreactive Intraepithelial Lymphocytes (IELs)
Genetic Features
HLA Genes
Non-HLA Genes
Environmental Influences
Gluten Proteins
Other Environmental Factors
In Vivo and In Vitro Models
Animal Models
Organ Culture Assays
Pathogenic Mechanisms
Gluten-reactive CD4+ T Cells
Role of Transglutaminase 2
Gluten Antigen Presentation by Disease-associated DQ Molecules
Mucosal Antigen-presenting Cells
Effector Mechanisms Leading to Mucosal Alterations
Autoantibodies as Potential Immunologic Markers
Serology
Staining of Immune Complexes
Treatment and Outcome
Current Treatment and Outcome
Novel Therapeutic Options
Concluding Remarks
-Future Prospects
Acknowledgments
References
60. Inflammatory Bowel Diseases / Lloyd Mayer
Introduction
History
Epidemiology and Environmental Factors
Clinical and Pathologic Features
Disease Presentation
Pathology
Genetics
Immunopathogenesis
Epithelial Barrier and Innate Immunity
Adaptive Immunity
Host-Microbial Interactions
Biomarkers
Fecal Markers
Serologic Markers
Treatment
Medical
Surgical
Future Prospects
References
61. Hepatitis / Giorgina Mieli-Vergani
Clinical, Pathologic, and Epidemiologic Features
Clinical Features
Pathologic Features
Epidemiologic Features
Autoimmune Features
Autoantibodies as Potential Immunologic Markers
Genetic Features
Animal Models
Pathologic Effector Mechanisms
Treatment and Outcome
Standard Treatment
Alternative Treatments
Duration of Treatment
Liver Transplantation
Future Treatment Approaches
Concluding Remarks
-Future Prospects
References
62. Primary Biliary Cirrhosis / M. Eric Gershwin
Clinical, Pathologic, and Epidemiologic Features
History
Diagnosis
Pathology
Clinical Features
Epidemiology and Natural History
Treatment
Autoimmune Features
Genetic Features
Familial PBC: Twins and Relatives
HLA Association
Genome-wide Association Studies (GWAS)
Epigenetic Effects
Fetal Microchimerism
Genes on the X Chromosome
Environmental Provocation of PBC
Infections
Xenobiotics
Experimental Animal Models
Pathologic Effector Mechanisms
Autoantibodies as Potential Immunologic Markers
Concluding Remarks
-Future Prospects
References
63. Primary Sclerosing Cholangitis / Keith D. Lindor
Epidemiology and Risk Factors
Epidemiologic Features
Risk Factors
Natural History, Clinical Features, and PSC-IBD
Natural History and Clinical Features
PSC-IBD
Diagnosis
Biochemical Features
Cholangiography
Histology
PSC Subtypes and Pediatric PSC
Small Duct PSC
PSC-AIH
Pediatric PSC
PSC-Associated Malignancies
Colorectal Neoplasia
Cholangiocarcinoma (CCA)
Gallbladder Neoplasia
Hepatocellular Carcinoma
Genetics
Animal Models
Overview
Summary of PSC Models
Potential Pathogenic Mechanisms
Overview
Bacterial Translocation, Pathogen-associated Molecular Patterns, and Innate Immune Response
Adhesion Molecules, Lymphocyte Homing, and the Liver-Gut Axis
Antibodies, Memory, and Regulatory T cells
Transporter Defects and Bile Acids
Autoimmune Features
Treatment
Medical Therapy
Therapeutic Endoscopy
Liver Transplantation
Concluding Remarks
References
64. Autoimmune Pancreatitis and IgG4-related Disease / Kendo Kiyosawa
Historical Background
Autoimmune Pancreatitis - Clinical, Pathologic, and Epidemiological Features
Clinical Features
Extra-pancreatic Lesions
Pathological Features
Epidemiologic Features
Autoimmune Features
Genetic Features
Animal Models
Pathological Mechanisms
Immunological Markers in Diagnosis
Treatment and Outcome
IgG4-related Disease
Definition
Historical Background
Epidemiology
Clinical Features of IgG4-relate4 Disease
Definite IgG4-related Diseases
Possible IgG4-related Diseases
Pathological Features
Autoimmune Features, Genetic Features, Animal Models, and Pathological Mechanisms
Diagnosis
Treatment
Concluding Remarks: Future Prospects
References
pt. 12 Skin Diseases
65. Autoimmune Bullous Skin Diseases-Pemphigus and Pemphigoid / Luis A. Diaz
Introduction
Pemphigus Vulgaris
Clinical, Pathologic, and Epidemiologic Features
Autoimmune Features
Genetic Features
In Vivo and In Vitro Models
Pathologic Effector Mechanisms
Autoantibodies as Potential Immunologic Markers
Pemphigus Foliaceus
Clinical, Pathologic, and Epidemiologic Features
Autoimmune Features
Genetic Features
In Vivo and In Vitro Models
Pathologic Effector Mechanisms
Autoantibodies as Potential Immunologic Markers
Environmental Factors involved in Fogo Selvagem
Other Types of Pemphigus
Paraneoplastic Pemphigus
Drug-induced Pemphigus
IgA Pemphigus
Bullous Pemphigoid
Clinical, Pathologic, and Epidemiologic Features
Autoimmune Features
Genetic Features
In Vivo and In Vitro Models
Pathologic Effector Mechanisms
Autoantibodies as Potential Immunologic Markers
Other Subepidermal Bullous Diseases
Herpes Gestationis (Pemphigoid Gestationis)
Cicatricial Pemphigoid
Linear IgA Disease
Epidermolysis Bullosa Acquisita
Dermatitis Herpetiformis
Treatment of Autoimmune Bullous Diseases
Concluding Remarks
References
66. Non-bullous Skin Diseases: Alopecia Areata, Vitiligo, Psoriasis, and Urticaria / David A. Norris
Alopecia Areata
Clinical, Pathologic, and Epidemiologic Features
Autoimmune Features
Genetic Features
In Vivo and In Vitro Models
Pathologic Effector Mechanisms
Autoantibodies as Potential Immunologic Markers
Concluding Remarks
-Future Prospects
Vitiligo
Clinical, Pathologic, and Epidemiologic Features
Autoimmune Features
Genetic Features
In Vivo and In Vitro Models
Pathogenetic Mechanism
Autoantibodies as Potential Immunologic Markers
Concluding Remarks
-Future Prospects
Psoriasis
Clinical, Pathologic, and Epidemiologic Features
Autoimmune Features
Genetic Features
In Vivo and In Vitro Models
Pathogenic Mechanism
Autoantibodies as Potential Immunologic Markers
Concluding Remarks
-Future Prospects
Chronic Urticaria
Clinical, Pathologic, and Epidemiologic Features
Autoimmune Features
Genetic Features
In Vivo and In Vitro Models
Pathologic Effector Mechanisms
Autoantibodies as Potential Immunologic Markers
Concluding Remarks
-Future Prospects
References
pt. 13 Nephropathies and Reproductive System
67. Autoimmune Disease in the Kidney / Ronald J. Falk
Introduction
Are there Hallmarks of Autoimmune Disease?
Autoantibodies and Their Antigens
Hallmarks of Autoimmune Diseases of the Kidney
Autoreactive T and B Cells Evade Deletion
Pre-existence of Asymptomatic "Normal" Autoantibodies
Hyperactivity of Fc-FcR Pathway
Antigenic Alterations of "Self" Proteins
Susceptibility to Environmental Impacts
Microbial Infections
Summary
Future Directions
References
68. Autoimmune Orchitis and Autoimmune Oophoritis / Kenneth S.K. Tung
Introduction
Experimental Autoimmune Disease of the Testis
Autoimmune Orchitis in the Dark Mink
Autoimmune Orchitis in Rats Expressing Transgenic Human HLA B27 and Human β2 Microglobulin
Post-vasectomy Autoimmune Orchitis in Mice with Treg Depletion and Post-vasectomy Tolerance to Testis Antigens
Autoimmune Orchitis Associated with Viral Infection
Autoimmune Orchitis in Day 3 Thymectomized (d3tx) Mice
Classical Experimental Autoimmune Orchitis Induced by Immunization with Testis Antigen in Adjuvant
Clinical Autoimmune Disease of the Testis
Idiopathic Male Infertility
Infertility and ASA Coexist with Other Autoimmune Diseases
Vasectomy, Sperm Granuloma, and Cystic Fibrosis
Orchitis Associated with Virus Infections
Experimental Autoimmune Disease of the Ovary
Spontaneous Autoimmune Ovarian Disease (AOD) in AIRE Null Mice
AOD in Day 3 Thymectomized (d3tx) Mice
AOD in Neonatal Mice by Maternal Antibody to Murine ZP3
Classical Experimental Autoimmune Oophoritis
Clinical Autoimmune Disease of the Ovary
Contents note continued: Concluding Remarks
Acknowledgments
References
pt. 14 Cardiovascular System and Lungs
69. Rheumatic Fever and Rheumatic Heart Disease / J. Kalil
Clinical, Pathological, and Epidemiologic Features
Autoimmune Features
Genetic Features
Innate Immune Response
Adaptive Immune Response
Both Innate and Adaptive Immune Response
In Vivo and In Vitro Models
In Vivo Model of Myocarditis and Valvulitis
In Vitro Model of Rheumatic Heart Disease Autoimmune Reactions
Pathologic Effector Mechanisms
Autoantibodies as Potential Immunologic Markers
Concluding Remarks
-Future Prospects
References
70. Myocarditis and Dilated Cardiomyopathy / Ziya Kaya
Historical Background
Clinical, Pathologic, and Epidemiologic Features
Myocarditis
Dilated Cardiomyopathy
Autoimmune Features and Immunologic Markers
Circulating Antibodies
Immunofluorescence
Western Immunoblot
Immunoassay with Defined Antigens
Immunologic Assessment of Biopsies
Genetic Features
Environmental Features
Animal Models and Pathogenic Mechanisms
Treatment and Outcome
Personal Thoughts
Acknowledgments
References
71. Atherosclerosis / Alex Bobik
Introduction
Development of Atherosclerotic Lesions
Mouse Models of Atherosclerosis
Culprit Autoantigens
Oxidized Low-density Lipoprotein (oxLDL)
Heat Shock Protein 60 (HSP60)
β2 Glycoprotein 1 (β2-GP1)
Immune Responses in Atherosclerosis
Innate Immunity in Atherosclerosis
Adaptive Immunity in Atherosclerosis
Other Key Cellular Players
Immune System Activation
Experimental Therapeutics: A Protective "Vaccine" for Atherosclerosis
Implications for Clinical Translation
References
72. Necrotizing Arteritis and Small Vessel Vasculitis / Ronald J. Falk
Historical Background
Necrotizing Arteritis
Purpura and Small Vessel Vasculitis
Polyarteritis Nodosa
Clinical, Epidemiologic, and Pathologic Features
Autoimmune Features
Genetic Features and Environmental Influences
In Vivo Models
Pathologic Effector Mechanisms
Autoantibodies as Potential Immunologic Markers
Kawasaki's Disease
Clinical, Pathologic, and Epidemiologic Features
Autoimmune Features
Genetic Features and Environmental Influences
In Vivo Models
Pathologic Effector Mechanisms
Autoantibodies as Potential Immunologic Markers
ANCA-Associated Vasculitis (AAV)
Clinical, Pathologic, and Epidemiologic Features
Autoimmune Features
Genetic Features
Environmental Influences
In Vivo Models
Pathologic Effector Mechanisms
Autoantibodies as Immunologic Markers
Cryoglobulinemic Vasculitis
Clinical, Pathologic, and Epidemiologic Features
Autoimmune Features
Genetic Features and Environmental Influences
In Vivo Models
Pathologic Effector Mechanisms
Autoantibodies as Immunologic Markers
IgA Vasculitis (Henoch
-Schonlein Purpura)
Clinical, Pathologic, and Epidemiologic Features
Autoimmune Features
Genetic Features and Environmental Influences
In Vivo Models
Pathologic Effector Mechanisms
Autoantibodies as Potential Immunologic Markers
Concluding Remarks
-Future Prospects
References
73. Large and Medium Vessel Vasculitides / Jorg J. Goronzy
Vasculitides of Large and Medium-sized Blood Vessels
Giant Cell Arteritis
Historical Background
Clinical, Pathologic, and Epidemiologic Features
Vascular Legion
Epidemiology
Genetic Features
Pathogenic Mechanisms
T Cells and Antigen-Presenting Cells in Giant Cell Arteritis
Macrophages in Giant Cell Arteritis
Intimal Hyperplasia
Immuno-stromal Interactions Promoting Vasculitis
Systemic Inflammatory Syndrome
Treatment, Monitoring, and Outcome
Takayasu's Arteritis
Historical Background
Clinical, Pathologic, and Epidemiologic Features
Genetic Features
Pathogenic Mechanisms
Treatment and Outcome
Concluding Remarks
-Future Perspectives
Acknowledgment
References
74. Idiopathic and Autoimmune Interstitial Lung Disease / Ronald G. Crystal
Introduction
History
Cryptogenic Organizing Pneumonia
Idiopathic Pulmonary Fibrosis
Clinical, Pathological, and Epidemiological Features
Cryptogenic Organizing Pneumonia
Idiopathic Pulmonary Fibrosis
Autoimmune Features
Cryptogenic Organizing Pneumonia
Idiopathic Pulmonary Fibrosis
Genetic Features
Cryptogenic Organizing Pneumonia
Idiopathic Pulmonary Fibrosis
In Vivo and In Vitro Models
Cryptogenic Organizing Pneumonia
Idiopathic Pulmonary Fibrosis
Pathologic Effector Mechanisms
Cryptogenic Organizing Pneumonia
Idiopathic Pulmonary Fibrosis
Treatment and Outcome
Cryptogenic Organizing Pneumonia
Idiopathic Pulmonary Fibrosis
Conclusions
Acknowledgments
References
pt. 15 Unclassified Expressions of Autoimmunity
75. Cameos: Candidates and Curiosities / Ian R. Mackay
Introduction
Autoimmune/Inflammatory Syndrome Induced by Adjuvants
Autonomic Neuropathy
Birdshot Retinopathy
Cystitis, Interstitial
Endometriosis
Epilepsy
Fatigue Syndrome
Folate Deficiency
Lichen Sclerosus
Lymphocytic Mastitis
Metabolic-Genetic Storage Diseases
Movement Disorders
Narcolepsy
Osteoarthritis
Parathyroid Disease
Polychondritis, Relapsing
Prostatitis
Sarcoidosis
References
76. Autoantibodies Against Cytokines / James W. Goding
Introduction
Autoantibodies Against Cytokines in Humans
Autoantibodies Against Type I and Type II Interferon
Autoantibodies Against IL-1 α
Autoantibodies Against Tumor Necrosis Factor (TNF)
Autoantibodies Against IL-6
Autoantibodies against Granulocyte-Macrophage Colony-Stimulating Factor
Pathogenicity of Autoantibodies Against Cytokines
-General Comments
Autoantibodies Against GM-CSF Cause Idiopathic Pulmonary Alveolar Proteinosis
Autoantibodies Against Erythropoietin Cause Pure Red Cell Aplasia
Autoantibodies Against IFN-γ Cause Mycobacteria Infections
Autoantibodies Against IL-17A, IL-17F, and IL-22 Correlate with Mucocutaneous Candidiasis in Autoimmune-Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy
Opportunistic Infections in Patients with a Thymoma
Autoantibodies Against the Bioactivity of Osteoprotegerin
Autoantibodies Against IL-8
Autoantibodies Against IL-1 α
Autoantibodies Against IL-6
What Is the Therapeutic Benefit of Autoantibodies against Cytokines from Pharmaceutically Prepared Immunoglobulin?
Are Anti-Cytokine Autoantibodies Against a Range of Cytokines in all Healthy Humans?
Analysis of a Panel of Neutralizing Monoclonal Antibodies to GM-CSF
Advantage of Studying Monoclonal Autoantibodies with Natural and Authentic H and L Chain Pairing
Autoantibodies Against GM-CSF Were all Polyclonal, Excluding a "Forbidden B Cell Clone"
No Preferred V-gene Usage in Autoantibodies to GM-CSF
Multiple Epitopes Recognized by Pathogenic Monoclonal Autoantibodies to GM-CSF
Mechanism of Pathogenicity of Monoclonal Autoantibodies to GM-CSF
Inhibitory Activity Is Strengthened by Formation of Stable High-avidity Complexes Comprising Multiple Antibodies Binding to Multiple Epitopes
Somatic Mutation of Autoantibodies to GM-CSF
Is Antibody Autoreactivity a Consequence of Somatic Mutation?
Could Autoantibodies Arise in Response to a B Cell Epitope on a Pathogen Antigen that Mimics a Self-antigen GM-CSF?
Autoantibodies to GM-CSF: Implications for B Cell Tolerance to Cytokines
General B Cell Tolerance
Antibodies Binding to Multiple Epitopes on GM-CSF Suggest that B Cells Lack Tolerance to Cytokines
Role of T Cells and the Thymus in Pathogenesis of Autoantibodies to Cytokines
General T Cell Tolerance
Role of the AIRE Gene in T Cell Tolerance
T Cell Tolerance to Cytokines
T Cell Tolerance Is Incomplete and Breakable
Autoantibodies against Cytokines in APECED
Autoantibodies against Cytokines in Patients with Thymoma
Induction of Autoantibodies as a Consequence o Therapy with Recombinant Cytokines
Conclusions and Future Prospects
References
pt. 16 Diagnosis, Prevention, and Therapy
77. Autoantibody Assays: Performance, Interpretation, and Standardization / Marvin J. Fritzler
Introduction
Spectrum of Autoantibodies
Assays and Technologies for Autoantibody Testing
Clinical Interpretation and Application of Autoantibody Testing
Clinical Practice Guidelines
Laboratory Reports, Electronic Medical Records, and Cost Analysis
Standardization and Quality Assurance
Conclusions and Future Prospects
References
78. Prediction of Autoimmune Disease / Roberto Gianani
Type 1 Diabetes Mellitus as a Model for Prediction of Autoimmune Disease
Pancreatic Pathology in Type 1 Diabetes Mellitus and Islet Autoimmunity
Genetics
Laboratory Markers of Autoimmunity (Including Autoantibodies and T Cell Assays)
Metabolic Studies
Organ-Specific Autoimmune Diseases
Thyroid
Addison's Disease
Celiac Disease
Multiple Sclerosis
Non-Organ Specific Disease
Rheumatoid Arthritis
Systemic Lupus Erythematosus
Conclusions
Acknowledgments
References
79. Prevention of Autoimmune Disease: The Type 1 Diabetes Paradigm / John M. Wentworth
Introduction
People at Risk for Type 1 Diabetes
Primary Prevention
Contents note continued: Diet and the Intestinal Environment
Viruses
Secondary Prevention
Mucosa-mediated Antigen-specific Tolerance
Trials of Islet Autoantigen-specific Vacc inationinHumans
Epilogue
Acknowledgments
References
80. Treatment of Autoimmune Disease: Established Therapies / Jennifer K. King
Principles of Immune Suppression
General Considerations
Non-Specific Anti-Inflammatory Drugs
NSAIDs
Glucocorticoids
Established Treatments of Rheumatic Diseases
Antimalarials
Sulfasalazine
Leflunomide
Methotrexate
Cyclophosphamide
Mycophenolate Mofetil (Cellcept)
Azathioprine (Imuran)
Cyclosporin A
Other Treatment Options
B Cell Suppressive Therapies
IVIG
Moving Towards Biological and Molecular Therapies
References
81. Treatment of Autoimmune Disease: Biological and Molecular Therapies / Lucienne Chatenoud
Introduction
Therapeutic Armamentarium Derived from Biotechnology
Monoclonal Antibodies (mAbs)
Other Soluble Receptors and Protein Fusion Conjugates
Soluble Autoantigens
Bone Marrow Transplantation
Cell Therapy and Gene Therapy
Cell Therapy
Gene Therapy
Perspectives for the Future
References.