Translational Autoimmunity, Volume 6: Advances in Autoimmune Rheumatic Diseases

Front Cover
Translational Autoimmunity: Advances in Autoimmune Rheumatic Diseases
Copyright
Dedication
Contents
Contributors
Preface
Series editor’s biography
Acknowledgment
Abbreviations
Chapter 1 Introduction on autoimmune rheumatic diseases
1 Introduction
2 ARD through the history
3 Diagnosis of ARD
4 Treatment of ARD
4.1 Pharmacological treatment
4.2 Exercise and physical activity
4.3 Microbiota modulation
4.4 Epigenetic modification
5 Conclusion
References
Chapter 2 Bone Health in autoimmune inflammatory rheumatic diseases
1 Introduction
2 Prevalence of bone health impairment in AIIRD
3 Risk factors for bone loss in AIIRD
3.1 General risk factors for bone loss, osteoporosis and fractures
3.2 Disease-related risk factors for bone loss, osteoporosis and fractures
4 Pathophysiology of bone loss in AIIRD
5 Evaluation and management of bone loss/osteoporosis in patients with AIIRD
6 Conclusion
References
Chapter 3 Rheumatic diseases: From bench to bedside
1 Introduction
2 Pathogenesis of autoimmunity in rheumatic diseases (AIRDs)
2.1 Molecular mimicry
2.2 Apoptosis and secondary necrosis from apoptosis
2.3 Neoantigens or autoantigens formation
2.4 Dysregulation of innate and adaptive immune system in autoimmunity
3 Comparisons of the immunopathogenesis in various autoimmune rheumatic diseases
4 The clinical implications of the immunopathogenesis of autoimmunity
4.1 Biomarkers in diagnosis and disease activity
4.2 Therapeutic implications
5 Conclusion
References
Chapter 4 Rheumatic fever: From pathogenesis to vaccine perspectives
1 Introduction
2 Diagnosis of acute rheumatic fever
3 Major manifestation
3.1 Carditis
3.2 Arthritis
3.3 Sydenham chorea
3.4 Erythema marginatum
3.5 Subcutaneous nodules
4 Minor manifestations
4.1 Arthralgia
4.2 Fever
4.3 Prolonged PR interval on electrocardiogram
4.4 Elevated acute phase reactants
4.5 Evidence of streptococcal infection
5 Treatment
5.1 Primary prevention (GAS pharyngitis treatment)
5.2 Manifestation treatment
5.2.1 Fever
5.2.2 Arthralgia and arthritis
5.2.3 Carditis
5.2.4 Chorea
5.2.5 Secondary prevention (recurrence prevention)
5.2.6 Vaccine development
6 Conclusion
References
Chapter 5 Changes in future rheumatoid arthritis treatment in the light of Epstein-Barr virus infection
1 Introduction
2 Epstein-Barr virus
3 Epstein-Barr virus infections
4 Associations between Epstein-Barr virus and rheumatoid arthritis disease
5 Current and future treatment of rheumatoid arthritis disease
6 Conclusion
References
Chapter 6 Rheumatic diseases: The microbiota-immunity axis in development and treatment
1 Introduction
2 The microbiota and the immune system crosstalk
2.1 The role of microbiota in immune-mediated disorders
2.2 The microbiota contribution to autoimmunity
3 Microbiota and autoimmune rheumatic diseases
3.1 Rheumatoid arthritis
3.2 Spondyloarthritis
3.3 Psoriatic arthritis
3.4 Systemic lupus erythematosus
3.5 Sjögren's syndrome
3.6 Systemic sclerosis
4 Microbiota shaping as a potential therapeutic target
4.1 Microbiota as a biomarker of response to treatment in rheumatic diseases
5 Conclusion
References
Chapter 7 The diagnostic laboratory tests in rheumatic diseases
1 Introduction
2 Acute-phase reactants
3 Laboratory tests in rheumatoid arthritis
4 Laboratory tests in spondyloarthritis
5 Laboratory tests in autoimmune connective tissue diseases
5.1 Systemic lupus erythematosus and antiphospholipid syndrome
5.2 Systemic sclerosis
5.3 Idiopathic inflammatory myopathies
5.4 Sjögren’s syndrome
5.5 Undifferentiated and overlapping connective tissue diseases
6 Laboratory tests in vasculitis
7 Laboratory tests in infectious arthritis
8 Laboratory tests in microcrystalline arthritis
9 Laboratory tests in osteoporosis
10 Laboratory tests in periodic fevers
11 Appendix: Analysis of the synovial fluid
12 Conclusion
References
Chapter 8 Autoantibody profiling in autoimmune rheumatic diseases: How research may translate into clinical practice
1 Introduction
2 The clinical rationale of autoantibody profiling
3 Proteomic technology for multiautoantibody profiling
4 Autoantibody profiling in autoimmune rheumatic diseases
4.1 Antibody profiling in systemic lupus erythematosus
4.2 Antibody profiling in the antiphospholipid syndrome
4.3 Antibody profiling in systemic sclerosis
4.4 Antibody profiling in autoimmune inflammatory myositis
5 Antibody profiling in rheumatoid arthritis
6 Autoantibody profiling in autoimmune organ-specific diseases
7 Analytical challenges of multiplex technology
8 Conclusion
References
Chapter 9 Air pollution and rheumatoid arthritis: Current knowledge and state of the art
1 Introduction
2 Overview of air pollution and its health effects
2.1 Definitions
2.2 Sources of air pollution
2.3 Molecular composition of air pollution
2.4 Health impact of air pollution exposure
3 Studies linking air pollution with rheumatoid arthritis
3.1 Studies reporting air pollution as a risk factor of rheumatoid arthritis
3.2 Studies reporting associations between air pollution and RA biomarkers or disease activity markers
3.2.1 Epidemiological studies
3.2.2 Laboratory study
4 Mechanisms potentially linking air pollution with rheumatoid arthritis
4.1 From exposure to the release of autoantibodies: Pre-RA phase
4.1.1 Oxidative stress
4.1.2 Formation of autoantigens
4.1.3 Production of autoantibodies
4.1.4 Inflammation
4.2 Arthritis: RA phase
5 Future directions
6 Conclusion
Acknowledgments
References
Chapter 10 Advanced therapies in rheumatoid arthritis
1 Introduction
2 Etiology and pathogenesis
3 Presentation
4 Articular features of RA
5 Extra-articular features of RA
6 Diagnosis
6.1 Blood tests
6.2 Radiological investigations
6.3 Diagnostic criteria
7 Management of the disease
7.1 General management, work and home life
7.2 Disease activity scoring
7.3 Pharmacological management
8 EULAR treatment recommendations
8.1 csDMARDS
8.1.1 Methotrexate
Mechanism of action
Administration
Indications
Contraindications
Evidence
8.1.2 Sulfasalazine
Mechanism of action
Administration
Indications
Evidence
8.1.3 Hydroxychloroquine
Mechanism of action
Administration
Indications
Evidence
8.1.4 Leflunomide
Mechanism of action
Administration
Indications
Contraindications
Evidence
8.2 Biologic DMARDS
8.2.1 TNF inhibitors (TNFi)
Mechanism of action
Administration
Indications
Contraindications
Evidence
8.2.2 Anti-B-cell agent (rituximab)
Mechanism of action
Administration
Indications
Contraindications
Evidence
8.2.3 IL-6 inhibitors (IL-6i)
Mechanism of action
Administration
Indications
Contraindications
Evidence
8.2.4 Costimulatory blockade (Abatacept)
Mechanism of action
Administration
Indications
Contraindications
Evidence
8.2.5 JAK inhibitors
Mechanism of action
Administration
Indications
Contraindications
Evidence
9 Horizon scanning for new agents
10 Conclusion
References
Chapter 11 A tolerogenic dendritic cell–based therapy targeting heat shock protein–specific regulatory T cells in rheumato ...
1 Introduction
2 Heat shock proteins
3 Preclinical and clinical studies of HSP-induced tolerance
4 Preclinical studies with tolDCs
5 Toward HSP-loaded tolDCs as a therapy for RA
6 Conclusion
References
Chapter 12 T-cell large granular lymphocytic leukemia in the setting of rheumatoid arthritis
1 Introduction
2 Epidemiology
3 Pathogenesis
4 Diagnosis
5 Clinical manifestations
6 Differential diagnosis
7 Treatment
8 Conclusion
References
Chapter 13 Biomaterials as tools for re-balancing skewed immunity in rheumatoid arthritis
1 Introduction
1.1 Rheumatoid arthritis
1.2 The skewed immunity in RA joint tissues
1.2.1 The innate immunity in RA inflammation
Neutrophils
Macrophages
Dendritic cells
Natural killer cells
Mast cells
1.2.2 Adaptive immunity in RA inflammation
B-Lymphocytes
Dendritic cells
T cells
1.2.3 The rich network composed of innate and adaptive immunity in RA development
1.3 Current clinical RA medicines and their impacts on immunity
1.3.1 DMARDs: Lowering the levels of proinflammatory cytokines
1.3.2 NSAIDs: Inhibiting inflammatory molecular pathways
1.3.3 GCs: Restricting phospholipid-related inflammation
1.3.4 Biological agents: Targeting inflammatory signals and immune cells
1.3.5 Combinatory use of multiple RA medicines for enhanced efficacy against RA
1.4 Biomaterials-assisted immune modulation
2 Biomaterials-based strategies for rebalancing the skewed RA immunity
2.1 Improving RA therapy by using the merits of classical biomaterials
2.1.1 Targeted reduction of RA inflammation by using biomaterials carriers
2.1.2 Controlled release of RA drugs from biomaterials for prolonged drug half-life
2.1.3 A synergistic antiinflammatory effect by using multiple drugs simultaneously
2.2 Trigger-responsive materials for “smart” RA treatment
2.3 Engineering live cells surfaces for improved in vivo delivery of RA drugs
2.4 Polarizing immune cell phenotypes by using biomaterials tools for improved RA therapy
2.5 Biomaterial-based portable therapies for RA treatment
3 Conclusion
References
Chapter 14 Immunopathogenesis of systemic lupus erythematosus
1 Introduction
2 Genetic factors in SLE
3 Epigenetic mechanisms in SLE
3.1 DNA methylation
3.2 Histone modifications
3.3 MicroRNAs
4 Environmental factors and gender in SLE
5 Apoptosis and SLE
6 The complement system and SLE
7 Toll-like receptors and SLE
8 Innate and adaptive immunity
8.1 Innate immune cells
8.1.1 Dendritic cells
8.1.2 Neutrophils
8.1.3 Monocytes
8.2 Adaptive immune cells
8.2.1 T lymphocytes
8.2.2 B lymphocytes
9 Tissue inflammation and clinical manifestations (organ-specific disease features)
9.1 Nephritis
9.2 Skin
9.3 CNS
10 Treatment
11 Conclusion
References
Chapter 15 Challenges in systemic lupus erythematosus: From bench to bedside
1 Introduction
2 Pathogenesis
2.1 Genetic susceptibility
2.2 Immune disturbance
2.3 Autoantibody production
2.4 Cytokine networks and immune cells
2.5 Environmental risk factors
2.6 Ultraviolet radiation (UVR) and climates
2.7 Viral infection
2.8 Drug-induced lupus erythematosus
2.9 Lifestyle factors
2.10 Occupational exposures
3 Diagnosis
4 Classification criteria
5 SLE phenotypes and key disease biomarkers
5.1 Antinuclear antibody
5.2 Anti-DNA
5.3 Antibodies to complement
5.4 Antiphospholipid antibodies
5.5 Serological vs. clinical activity
6 Management
7 Management of cardiovascular disease risk
8 Management of lupus nephritis (LN)
9 Management of refractory SLE with a focus on phase 2/3 clinical trials
9.1 Targeted biological therapies
9.2 Targeting B cells
9.3 Targeting interferon
9.4 Targeting plasmacytoid dendritic cells (pDCs)
10 Conclusion
Acknowledgments
References
Chapter 16 Therapeutic potential of the current options in treating systemic lupus erythematosus: Challenges and prospective
1 Introduction
2 SLE progression and factors affecting it
2.1 Role of genetics in SLE
2.2 The role of hormonal and environmental factors
2.3 Apoptosis
3 Therapeutic options for SLE
3.1 Antimalarials
3.2 Glucocorticosteroids
3.3 Immunosuppressant’s
3.4 Biological agents for SLE
4 Current strategies to combat ADS
5 Conclusion
References
Chapter 17 The pathology and potential clinical applicability of interfering T cells in systemic lupus erythematosus
1 Introduction
2 Pivotal immunologic players in SLE pathophysiology
3 Physiology and anatomy of T cells
3.1 T-cell development—From bone marrow, thymus to the periphery
3.2 Functional anatomy and physiology of T cells after leaving the thymus
3.3 Altered signaling pathways of lupus T cells
3.4 Metabolism and its alterations in lupus T cells
3.5 Diversity of T-cell subsets
3.5.1 CD4 + T cells (Th1, Th2, and Th17) and their alterations in SLE
Th1
Th2
Th17
3.5.2 Th9—A newly identified Th subset
3.5.3 Follicular T helper cells
3.5.4 Circulating Tfh cells
3.5.5 CD8 + T cells
3.5.6 NK and NKT cells
3.6 Regulatory T cells (CD4 +, CD8 + and γ δ regulatory T cells)
3.6.1 CD4 + regulatory T cells
3.6.2 CD8 + regulatory T cells
3.6.3 γ δ regulatory T cells
4 Current and evaluated therapies of SLE that manipulate T-cell physiology
4.1 Calcineurin inhibitors
4.2 Rapamycin
4.3 Anti-CD40L
4.4 N -acetylcysteine
4.5 Low-dose IL-2
5 Phenotypic and functional change of T-cell subsets after B-cell depletion
6 Conclusion
References
Chapter 18 Rheumatic chorea
1 Introduction
2 Pathophysiology
2.1 RC autoimmune molecular pathophysiology
2.2 Fronto-striatal dysfunction in RC
2.3 Genetics in RF and RC
3 Clinical features
4 Treatment options
4.1 Antibiotic treatment
4.2 Symptomatic treatment
4.3 Immunomodulatory treatment
5 Conclusion
References
Chapter 19 Evaluation and surgical management of the rheumatoid foot and ankle
1 Introduction
2 History and physical exam
3 Preoperative considerations
4 Vascular evaluation in the rheumatoid patient
5 Preoperative testing
6 Preoperative medication considerations
7 Venous thromboembolism prophylaxis
8 Foot and ankle manifestations of rheumatoid arthritis
9 Extraarticular and soft-tissue disorders
10 Pathomechanics
10.1 Forefoot
10.2 Synovectomy
11 Forefoot reconstruction
11.1 1st MTPJ
11.2 Lesser MTPJ’s and toes
12 Midfoot
13 Rearfoot
14 Ankle
14.1 Total ankle replacement in rheumatoid arthritis
14.2 Bone quality, total ankle replacement, and the rheumatoid patient
14.3 Ankle deformity in rheumatoid arthritis amenable to total ankle replacement
14.4 Considerations for surgical approach to total ankle replacement in RA
14.5 Revision total ankle arthroplasty in RA
15 Conclusion
References
Further reading
Chapter 20 Immunopathogenesis and treatment of scleroderma
1 Introduction
2 Pathogenesis
2.1 Genetic factors
2.2 Environmental factors
2.3 Vasculopathy
2.4 Immunological factors
3 Treatment
3.1 Treatment of morphea
3.2 Treatment of multiorgan SSc
3.2.1 Managing vascular manifestations
3.2.2 Immunosuppressive agents
3.2.3 Targeted therapy
4 Conclusion
Acknowledgment
References
Chapter 21 Skin manifestations and autoimmune disturbances in dermatomyositis
1 Introduction
2 Cutaneous manifestations of DM correlate with specific autoantibodies
2.1 Anti-Mi-2 phenotype
2.2 Anti-MDA5 phenotype
2.3 Anti-TIF1- γ phenotype
2.4 Anti-NXP2 phenotype
2.5 Anti-SAE phenotype
2.6 Anti-ARS phenotypes
3 Myositis-specific autoantibodies in a new classification system
4 Conclusion
References
Chapter 22 T cells in the pathogenesis of systemic sclerosis
1 Introduction
2 Pathogenesis of systemic sclerosis
3 T cells: A brief overview
4 T cells in systemic sclerosis
5 Th2/Th1 balance in systemic sclerosis
6 Th17 cells
7 Regulatory T cells (Tregs) and Tregs/Th17 balance
8 Tfh cells
9 Other Th subsets
10 Unconventional T cells
11 Angiogenic T cells
12 T cells and vasculopathy
13 Lessons from animal models of scleroderma
14 Immunotherapy and future prospects
15 Conclusion
References
Chapter 23 Etiopathogenesis of Behçet’s syndrome: The role of infectious, genetic, and immunological environmental factors
1 Introduction
2 Microbial etiology
3 Genetic etiology
4 Epigenetic contribution
5 Immunological etiology
6 Additional triggering factors
7 Conclusion
References
Chapter 24 Interleukin-1 family in Behçet’s disease: Inflammatory and antiinflammatory mediators
1 Introduction
2 The biological characteristics of IL-1 family cytokines
3 The association of IL-1 family genes and BD
4 Expression and function of IL-1 family cytokines in BD
4.1 The expression and function of IL-1 β in BD
4.2 The expression and function of IL-33 in BD
4.2.1 Regulatory T (Treg) cells and IL-33 expression
4.2.2 IL-33 in tissue remodeling and regeneration
4.2.3 The expression and function of IL-33 in BD
IL-33 and its receptor ST2 in the peripheral circulation and skin lesions
IL-33 and its receptor ST2 in the cerebrospinal fluid
4.2.4 IL-33 in Behçet’s disease
4.3 The expression and function of IL-18 in BD
4.4 The involvement of IL-36, IL-37, and IL-38 in BD
4.4.1 Interleukin-37: A new target for the treatment of Behçet disease
4.4.2 New IL-1 family members: IL-36 and IL-38
5 Clinical application and participation of IL-1 family cytokines in BD
6 Conclusion
References
Chapter 25 Salivary gland regeneration and repair in Sjögren’s syndrome
1 Introduction
1.1 Demographics
1.2 Etiopathogenesis
1.3 Clinical features
2 Salivary glands in Sjögren’s syndrome
2.1 Salivary gland—Anatomy and physiology
2.2 Xerostomia and therapy in Sjögren’s syndrome
3 Regenerative medicine
4 Regeneration of salivary glands
4.1 Stem cell transplantation
4.1.1 Autologous transplantation of salivary gland epithelial cells
4.1.2 Transplantation of nonepithelial cells
Mesenchymal stem cells
Induced pluripotent stem cells
4.2 Tissue engineering
4.3 Gene therapy
5 Conclusion
References
Chapter 26 Regulation of bone and joint inflammation by type 2 innate lymphoid cells
1 Introduction
2 Rheumatoid arthritis and T cell
3 Rheumatoid arthritis and ILC
4 Spondyloarthritis and ILCs
5 Role of ILC2 on the initiation phase of arthritis
6 Bone homeostasis and cytokines mediated by T cell
7 Bone homeostasis and ILC
8 Conclusion
References
Chapter 27 Arboviruses ( Alphavirus) related to autoimmune rheumatic diseases: Triggers and possible therapeutic interventions
1 Introduction
1.1 Alphavirus overview
2 Chikungunya virus (CHIKV)
2.1 General aspects
2.2 Clinical manifestations of CHIKV infection
2.3 Immune response against CHIKV and rheumatoid arthritis
3 O’nyong-nyong virus (ONNV)
3.1 General aspects
3.2 Clinical manifestations of ONNV infection
3.3 Immune response against ONNV and rheumatoid arthritis
4 Ross River virus (RRV)
4.1 General aspects
4.2 Clinical manifestations of RRV infection
4.3 Immune response against RRV and rheumatoid arthritis
5 Barmah Forest virus (BFV)
5.1 General aspects
5.2 Clinical manifestations of BFV infection
5.3 Immune response against BFV and rheumatoid arthritis
6 Mayaro virus (MAYV)
6.1 General aspects
6.2 Clinical manifestations of MAYV infection
6.3 Immune response against MAYV and rheumatoid arthritis
7 Sindbis virus (SINV)
7.1 General aspects
7.2 Clinical manifestations of SINV infection
7.3 Immune response against SINV and rheumatoid arthritis
8 Interface of possible treatments for alphaviruses in rheumatoid arthritis
9 Conclusion
References
Chapter 28 Rheumatologic manifestations of autoinflammatory diseases
1 Introduction
2 Familial Mediterranean fever (FMF)
2.1 Background
2.2 Clinical presentation
2.3 Fever
2.4 Pleuritis
2.5 Pericarditis
2.6 Peritonitis
2.7 Musculoskeletal manifestations
2.8 Skin manifestations
2.9 Neurologic manifestations
2.10 Amyloidosis
2.11 Other manifestations
3 Mevalonate kinase deficiency (MKD)
3.1 Background
3.2 Clinical presentation of HIDS phenotype
3.3 Fever
3.4 Lymphadenopathy and hepatosplenomegaly
3.5 Gastrointestinal manifestations
3.6 Musculoskeletal manifestations
3.7 Cutaneous and mucocutaneous manifestations
3.8 Neurologic manifestations
3.9 Macrophage activation syndrome
3.10 Amyloidosis
3.11 Other manifestations
3.12 Clinical presentation of MA phenotype
4 Tumor necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS)
4.1 Background
4.2 Clinical presentation
4.3 Fever
4.4 Skin manifestations
4.5 Gastrointestinal manifestations
4.6 Musculoskeletal manifestations
4.7 Ocular manifestations
4.8 Cardiorespiratory manifestations
4.9 Neurologic manifestations
4.10 Amyloidosis
4.11 Other manifestations
5 Cryopyrin-associated periodic syndromes (CAPS)
5.1 Background
5.2 Clinical manifestations
5.3 Fever
5.4 Cutaneous manifestations
5.5 Ocular manifestations
5.6 Otologic manifestations
5.7 Musculoskeletal manifestations
5.8 CNS manifestations
5.9 Amyloidosis
5.10 Other manifestations
6 Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome
6.1 Background
6.2 Clinical manifestations
6.3 Fever
6.4 Pharyngitis
6.5 Cervical adenitis
6.6 Aphthous stomatitis
6.7 Other manifestations
7 Conclusion
References
Index
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