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Dedication; Contents; Chapter 1: A History of Deimination Research in Japan: The Founding Fathers; References; Chapter 2: Aspects of Peptidylarginine Deiminase Regulation that May Predispose to Autoreactivity Against Citrullinated Proteins; 2.1 Summary; 2.2 Tolerance and Autoimmunity; 2.3 Discovery of Arginine Deimination; 2.4 Role of PAD4 in Innate Immune Responses; 2.5 PAD4 and NETs; 2.6 NETs in Autoimmunity; 2.7 Model of PAD4 Activation in the Pathogenesis of Autoimmune Disease; References; Chapter 3: Structures and Functions of Peptidylarginine Deiminases; 3.1 Introduction
3.2 PAD Isozymes: Similarities and Differences3.2.1 Overall Folds; 3.2.2 Structures and the Functions of the Catalytic Domains; 3.2.3 Ca2+-Binding Sites and Functions; 3.2.4 Structures and the Functions of N-Terminal Ig-Like Domain; 3.3 Application of PAD Structures for Drug Design; 3.4 Conclusions; References; Chapter 4: The Use of Genetically Engineered Mice to Study PAD Biology and Pathology; 4.1 Introduction; 4.2 PAD2; 4.3 PAD3; 4.4 PAD4; 4.5 PAD6; 4.6 Conclusions; References; Chapter 5: PAD Activation in Arthritis; 5.1 Introduction; 5.2 Methods to Determine PAD Activity
5.3 PAD Substrate Specificity5.4 PAD Isoforms Involved in Arthritis; 5.4.1 PAD2 and PAD4 Expression in Hematopoietic Cells; 5.4.2 PAD2 and PAD4 Expression in Joints; 5.5 PAD Activation; 5.5.1 Calcium; 5.5.2 Reducing Conditions; 5.6 PAD and NETosis; 5.7 PAD Activation and Citrullination in Relation to Inflammation in RA; 5.8 Citrullinated Proteins in Synovial Fluid; 5.9 Concluding Remarks; References; Chapter 6: Rheumatoid Arthritis: Transition from Systemic Autoimmunity to Joint Inflammation and Bone Loss; 6.1 Introduction
6.2 The Immune System Might Be Primed Against Citrullinated Autoantigens at Mucosal Extra-Articular Sites6.3 Autoimmunity Against Citrullinated Proteins Gradually Develops and Precedes Chronic Joint Inflammation; 6.4 ACPAs Target Maturing Osteoclasts Leading to Bone Loss and Pain in the Absence of Inflammation; 6.5 Summary; References; Chapter 7: Porphyromonas gingivalis Peptidyl Arginine Deiminase: A Unique Bacterial PAD with Implications for Periodontal Disease and Rheumatoid Arthritis; 7.1 Introduction; 7.2 Epidemiology, Etiology, and Clinical Features of PD
7.3 Oral Cavity Colonization and PD7.4 Porphyromonas gingivalis Is a Main Causative Agent of PD in Adult Population; 7.5 Citrullination Is a Posttranslational Modification Catalyzed by Peptidyl Arginine Deiminases; 7.5.1 Citrullination Catalyzed by PAD/PADI Is a Common Physiological Protein Modification; 7.5.2 Citrullination Catalyzed by PAD/PADI Is Implicated in the Pathogenesis of Several Diseases; 7.5.3 Citrullination Catalyzed by PPAD Is a Unique Feature of P. gingivalis; 7.5.4 Biochemical Properties of PPAD; 7.5.5 The Facts and Hypotheses on PPAD Implication in the Pathogenesis of PD
3.2 PAD Isozymes: Similarities and Differences3.2.1 Overall Folds; 3.2.2 Structures and the Functions of the Catalytic Domains; 3.2.3 Ca2+-Binding Sites and Functions; 3.2.4 Structures and the Functions of N-Terminal Ig-Like Domain; 3.3 Application of PAD Structures for Drug Design; 3.4 Conclusions; References; Chapter 4: The Use of Genetically Engineered Mice to Study PAD Biology and Pathology; 4.1 Introduction; 4.2 PAD2; 4.3 PAD3; 4.4 PAD4; 4.5 PAD6; 4.6 Conclusions; References; Chapter 5: PAD Activation in Arthritis; 5.1 Introduction; 5.2 Methods to Determine PAD Activity
5.3 PAD Substrate Specificity5.4 PAD Isoforms Involved in Arthritis; 5.4.1 PAD2 and PAD4 Expression in Hematopoietic Cells; 5.4.2 PAD2 and PAD4 Expression in Joints; 5.5 PAD Activation; 5.5.1 Calcium; 5.5.2 Reducing Conditions; 5.6 PAD and NETosis; 5.7 PAD Activation and Citrullination in Relation to Inflammation in RA; 5.8 Citrullinated Proteins in Synovial Fluid; 5.9 Concluding Remarks; References; Chapter 6: Rheumatoid Arthritis: Transition from Systemic Autoimmunity to Joint Inflammation and Bone Loss; 6.1 Introduction
6.2 The Immune System Might Be Primed Against Citrullinated Autoantigens at Mucosal Extra-Articular Sites6.3 Autoimmunity Against Citrullinated Proteins Gradually Develops and Precedes Chronic Joint Inflammation; 6.4 ACPAs Target Maturing Osteoclasts Leading to Bone Loss and Pain in the Absence of Inflammation; 6.5 Summary; References; Chapter 7: Porphyromonas gingivalis Peptidyl Arginine Deiminase: A Unique Bacterial PAD with Implications for Periodontal Disease and Rheumatoid Arthritis; 7.1 Introduction; 7.2 Epidemiology, Etiology, and Clinical Features of PD
7.3 Oral Cavity Colonization and PD7.4 Porphyromonas gingivalis Is a Main Causative Agent of PD in Adult Population; 7.5 Citrullination Is a Posttranslational Modification Catalyzed by Peptidyl Arginine Deiminases; 7.5.1 Citrullination Catalyzed by PAD/PADI Is a Common Physiological Protein Modification; 7.5.2 Citrullination Catalyzed by PAD/PADI Is Implicated in the Pathogenesis of Several Diseases; 7.5.3 Citrullination Catalyzed by PPAD Is a Unique Feature of P. gingivalis; 7.5.4 Biochemical Properties of PPAD; 7.5.5 The Facts and Hypotheses on PPAD Implication in the Pathogenesis of PD