Ankylosing Spondylitis - Axial Spondyloarthritis: Cellular, Molecular and Environmental Factors

Preface
Contents
About the Editor
Part I: Introduction
	1: An Overview to Ankylosing Spondylitis and Spondyloarthropathies
		1.1	 History
		1.2	 Epidemiology
		1.3	 Clinical Manifestation
			1.3.1	 General Symptoms, Spondylitis and Arthritis
			1.3.2	 Extra-Articular Manifestations
			1.3.3	 Complications and Co-morbidities
		1.4	 Diagnosis
			1.4.1	 History and Physical Examination
			1.4.2	 Lab Test
			1.4.3	 Imaging
				1.4.3.1	 Plain Radiography
				1.4.3.2	 Computed Tomography
				1.4.3.3	 Magnetic Resonance Imaging
			1.4.4	 Classification and Diagnostic Criteria
		1.5	 Pathogenesis
		1.6	 Treatment
			1.6.1	 Nonsteroidal Anti-Inflammatory Drugs
			1.6.2	 Glucocorticoids
			1.6.3	 Disease-Modifying Anti-Rheumatic Drugs
		1.7	 Conclusion
		References
Part II: Cells and Cytokines
	2: Innate Immune-Related Cells and Cytokines in Spondyloarthropathies
		2.1	 Introduction
		2.2	 Innate Immunity Components
			2.2.1	 Pattern Recognition Receptors (PRR)
				2.2.1.1	 Toll-Like Receptors (TLRs)
				2.2.1.2	 NOD-Like Receptors (NLRs)
			2.2.2	 Innate Cytokines
				2.2.2.1	 IL-1 Family
					2.2.2.1.1 IL-1 and Receptors
					2.2.2.1.2 IL-37
				2.2.2.2	 TNF and Receptors
				2.2.2.3	 IL-23 and Receptor
			2.2.3	 Soluble Components of Innate Immunity
				2.2.3.1	 Defensins
				2.2.3.2	 Complement System
			2.2.4	 Innate Immune Cells
				2.2.4.1	 Dendritic Cells (DC)
				2.2.4.2	 Macrophage Cells
				2.2.4.3	 Natural Killer (NK) Cells
		References
	3: Adaptive Immune-Related Cells and Cytokines in Spondyloarthropathies
		3.1	 Adaptive immunity in autoimmune disorders
		3.2	 The Pathogenic Role of Adaptive Immune Lymphocytes in SpAs
		3.3	 T Cell Activation, Signaling, and Cytokines in SpAs
			3.3.1	 Th1 and Th2 role in SpAs
			3.3.2	 Th17 and IL-17 in SpAs
				3.3.2.1	 IL-17 and Enthesitis
				3.3.2.2	 IL-17 and Bone Remodeling
				3.3.2.3	 Targeting Th17 in SpAs
			3.3.3	 Th22 and IL-22 in SpAs
			3.3.4	 Functional Abnormalities of Regulatory T Cells in SpAs
			3.3.5	 Cytotoxic T Cell in SpAs
			3.3.6	 Gamma Delta T Cells and SpAs
		3.4	 B Cell Activation and Signaling
		3.5	 Conclusions and Future Directions
		References
Part III: Genes
	4: Association of HLA and HLA-Related Genes with Ankylosing Spondylitis
		4.1	 Biology of HLA Expression and Functions
			4.1.1	 Genomic Organization
				4.1.1.1	 HLA Nomenclature
			4.1.2	 Molecular Structure
				4.1.2.1	 Molecular Structure of HLA-Class I
				4.1.2.2	 Molecular Structure of HLA-Class II
			4.1.3	 Pathways of Antigen Presentation
				4.1.3.1	 Processing and Presentation of Endocytosed Antigens
				4.1.3.2	 Processing and Presentation of Cytosolic Antigens
		4.2	 Association of HLA loci with Ankylosing Spondylitis
			4.2.1	 HLA-B27
				4.2.1.1	 Arthritogenic Peptide Hypothesis
				4.2.1.2	 HLA-B27 Misfolding Hypothesis
				4.2.1.3	 HLA-B27 Dimer Hypothesis
			4.2.2	 HLA Genes Other Than HLA-B27
		4.3	 Association of HLA-Related Genes with Ankylosing Spondylitis
			4.3.1	 Transporters in Antigen Presenting (TAP)
			4.3.2	 M1 zinc-Aminopeptidases
				4.3.2.1	 Endoplasmic Reticulum Aminopeptidase (ERAP)-1
				4.3.2.2	 ERAP2
				4.3.2.3	 NPEPPS
				4.3.2.4	 Ubiquitinases
				4.3.2.5	 LMP2
		4.4	 Role of Epigenetics in Ankylosing Spondylitis Pathogenesis
			4.4.1	 DNA Methylation
			4.4.2	 Histone Modifications
			4.4.3	 MicroRNAs
		References
	5: Association of Non-HLA Genes with Ankylosing Spondylitis
		5.1	 Cytokines and Cytokine-Receptors
			5.1.1	 IL-1RN Gene
			5.1.2	 IL-6 Receptor Gene
			5.1.3	 IL-12B Gene
			5.1.4	 IL-17 Gene
			5.1.5	 IL-23 and IL-23 Receptor
			5.1.6	 TNF and TNF Receptor
			5.1.7	 IL-10 Gene
		5.2	 Overview on Signal Transduction
			5.2.1	 VDR Gene
			5.2.2	 TLR4 Gene
			5.2.3	 G Protein-Coupled Receptor Gene
			5.2.4	 CTLA-4 Gene
			5.2.5	 PD-1 Gene
			5.2.6	 PTPN22 Gene
			5.2.7	 CARD9 Gene
			5.2.8	 TBKBP1 Gene
			5.2.9	 TRADD Gene
			5.2.10	 STAT3 Gene
			5.2.11	 STAT4 Gene
			5.2.12	 RUNX3 Gene
			5.2.13	 TBX21 Gene
			5.2.14	 Ancillary Mediators Involved in Lymphocyte Differentiation
		5.3	 Other Associated Genes with AS Disease
			5.3.1	 ANTXR2
			5.3.2	 SNAPC4
			5.3.3	 KIF21B
			5.3.4	 PTGER4
			5.3.5	 PPARGC1B
			5.3.6	 ANO6 Gene
			5.3.7	 Β-Defensin Gene Clusters
			5.3.8	 Pentraxin3
			5.3.9	 MIF Gene
			5.3.10	 BCL11B
			5.3.11	 Autophagy-Related Genes
		References
Part IV: Environmental Factors
	6: Spondyloarthropathies and Gut Microbiota
		6.1	 Introduction
		6.2	 Gut Microbiome
		6.3	 Spondyloarthropathies and Microbes
		6.4	 Spondyloarthropathies and Inflammatory Bowel Diseases
		6.5	 Animal Models of SpA and Gut Immunity
		6.6	 Dysbiosis and Inflammation in SpA
		6.7	 HLA-B27
		6.8	 Cytokines Induction by Microbiome
		6.9	 Probiotics and Prebiotics
		6.10	 Antibiotics and Fecal Transplant
		6.11	 Conclusion
		References
	7: Spondyloarthropathies and Food Intake
		7.1	 Introduction
			7.1.1	 Spondyloarthropathies
			7.1.2	 Ankylosing Spondylitis
		7.2	 Vitamins
			7.2.1	 Vitamin D
			7.2.2	 Other Vitamins
				7.2.2.1	 Vitamin E
				7.2.2.2	 Vitamin A
		7.3	 Low Starch Diet and Klebsiella
		7.4	 Fatty Acids
		7.5	 Obesity
		7.6	 Food Allergy
		7.7	 Conclusion
		References
	8: Spondyloarthropathies and Environmental Stresses
		8.1	 Introduction
		8.2	 Biomechanical Stress
		8.3	 Psychological Stress
		8.4	 Oxidative Stress
		8.5	 Smoking
		8.6	 Vaccination
		References
Index