Molecular Mechanisms of Spondyloarthropathies

ISBN-13: 9781441902979 / Angielski / Twarda / 2009 / 314 str.

Carlos Loppez-Larrea; Carlos La3pez-Larrea; Roberto Da-Az-Peaa

Opis

It is now over ten years since we edited the first edition of HLA-B27 in the Development of Spondyloarthropathies (SpA). It is obvious that over this period an enormous amount of information concerning SpA and HLA-B27 has accumulated, and this has been reflected in the knowledge of molecular mechanism of the spondyloarthropathies. Discussion for such a book took initial form at the outstanding 4th Gent Symposium on SpA in October 2006, but was not formally commissioned by Landes Bioscience until early 2007. Molecular Mechanisms of Spondyloarthropathies aims to synthesize this growing knowledge and present all the current studies concerning the basic research of SpA. Over the last decade, enormous progress has been made in the understanding of the molecular and cellular processes that lead to disease pathology. Recognition of the pathways involved in the pathogenic mechanisms of disease and the potential to target specific immune effector functions have opened the door to a wide range of innovative treatment opportunities for the SpA. Thus, we believe that the understanding of the specific molecular mechanisms involved would help to design highly specific drugs in the future. The contributors are among the best in their field and reflect the state of the art of research and current opinion of rheumatologists and immunologists.

Spis treści

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

O autorze

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.