Molecular Mechanisms of Spondyloarthropathies (eBook)

CARLOS LÓPEZ-LARREA is Professor of Immunology (UC M, Madrid, Spain) and currently Head of the Histocompatiblity Unit at the “Hospital Universitario Central de Asturias” (Oviedo, Spain). He is a world expert on spondyloarthropathies (SpA), in particular genetic (MHC) and immunologic factors that influence the development of SpA. His primary research is focused on understanding the role of HLA-B27 polymorphism in the development of ankylosing spondylitis (AS), and describing relevant associations of B27 subtypes with AS in large extended worldwide populations. In the last decade, the availability of HLA-B27 subtypes differentially associated with the disease has provided a unique tool for exploring the relationship between peptide specificity and pathogenetic potential. The main research interests of his group currently include the role of innate immunity (NKs) in SpA. He is a member of several national and international scientific organizations. It is now over ten years since the first edition of HLA-B27 in the Developement of Spondyloarthropathies (SpA) was published and edited by C. López-Larrea. This current book aims to synthesize the growing knowledge in the field and present all current studies concerning basic research in SpA.ROBERTO DÍAZ -PEÑA is a predoctoral investigator in the Histocompatibility Unit of the Department of Immunology, Hospital Universitario Central de Asturias. He graduated in biochemistry, at the University of Oviedo, Spain. His main research interests include the genetics of spondyloarthropathies, especially ankylosing spondylitis, and the role of inhibitory and activating KIR receptors in this disease.

1. Clinical Assessment in the Spondyloarthropathies...... 1
Ruth Wittoek and Herman Mielants
Abstract...... 1
Introduction...... 1
Ankylosing Spondylitis...... 2
Psoriatic Arthritis...... 9
2. Imaging in Spondyloarthritis...... 17
Walter P. Maksymowych
Abstract...... 17
Introduction...... 17
Plain Radiography......18
Computed Tomography...... 21
Isotopic Imaging...... 21
Ultrasound...... 22
Magnetic Resonance Imaging......22
Sacroiliac Joint...... 24
Spine...... 27
Conclusions...... 33
3. Spondyloarthritis, Diffuse Idiopathic Skeletal Hyperostosis (DISH) and Chondrocalcinosis...... 37
Jácome Brüges Armas, Ana Rita Couto and Bruno Filipe Bettencourt
Abstract......37
Introduction...... 37
Spondyloarthritis...... 37
Diffuse Idiopathic Skeletal Hyperostosis (DISH)...... 40
Chondrocalcinosis/Crystal Deposition Disease (Cppd CD)...... 40
Molecular Genetics...... 42
Conclusions...... 47
4. The Enthesis Organ Concept and its Relevance to the Spondyloarthropathies......57
Michael Benjamin and Dennis McGonagle
Abstract...... 57
Introduction...... 58
Enthesis Organ Structure...... 58
Mechanisms for Reducing Stress Concentration at the Enthesis Itself......63
Related Concepts...... 66
Conclusions...... 67
5. Synovial and Mucosal Imunopathology in Spondyloarthritis...... 71
Bernard Vandooren, Paul P. Tak and Dominique Baeten
Abstract...... 71
Introduction...... 71
Axial Versus Peripheral Spondyloarthritis...... 73
Skeletal Remodeling in Spondyoarthritis...... 73
Synovial Biomarkers in Spondyoarthritis...... 75
Gut Inflammation in Spondyloarthritis......76
The Pathogenesis of Spondyloarthritis: The Mucosa Hypothesis...... 77
Innate Immunity and Mucosal Inflammation...... 77
Adaptive Immunity and Mucosal Inflammation...... 78
The Pathogenesis of Joint Inflammation...... 78
Conclusions...... 79
6. Bone Loss in theSpondyloarthropathies: Role of Osteoclast, Rankl, Rank and Opg in the Spondyloarthropathies...... 85
Allen P. Anandarajah and Edward M. Schwarz
Abstract...... 85
Introduction...... 85
Pathogenesis of Bone Loss...... 86
Bone Loss in the Spondyloarthritis...... 91
Bone Loss in Ankylosing Spondylitis...... 91
Bone Loss in PsA...... 93
Bone Loss in Enteropathic Arthritis...... 93
Bone Loss in Reactive Arthritis...... 95
Conclusions...... 95
7. RankL/Rank as Key Fa ctors for Osteoclast Development and Bone Loss in Arthropathies...... 100
Andreas Leibbrandt and Josef M. Penninger
Abstract...... 100
Introduction...... 100
Basic Characteristics of the Rankl-Rank-Opg Axis...... 101
RANKL-RANK-OPG Interactions and Bone Remodeling......104
RANK(L) Signaling Pathways...... 104
Modulators of Rankl-Mediated Osteoclastogenesis...... 107
Rank-Rankl as Therapeutic Targets for Arthropathies......109
Conclusions...... 110
8. Bone Formation Versus Bone Resorption in Ankylosing Spondylitis......114
Georg Schett
Abstract...... 114
Introduction...... 114
Lessons from Rheumatoid Arthritis...... 114
Structural Damage in Ankylosing Spondylitis...... 115
Mechanism of Joint Formation—Molecular Lessons for Joint Fusion......115
Bony Protrusion as a Stress Response of the Joint...... 115
Osteoblast—the Bone Forming Cells...... 116
From the Osteoblast to the Osteophyte...... 116
Molecular Regulation of Osteophytes......116
Concepts of Osteophyte Formation...... 117
Why do Osteophytes Grow in aS and not in ra?...... 118
Conclusions...... 120
9. Biomarkers in Spondyloarthropathies...... 122
Chun-Hsiung Chen, David Tak Yan Yu and Chung-Tei Chou
Abstract...... 122
Introduction...... 122
Purpose of Developing Biomarkers in Ankylosing Spondyltis...... 122
How do Investigators Assess the Degree of Usefulness of Spondylitis Biomarkers?...... 125
Matrix