Pathogenesis of ankylosing spondylitis

• Published in: Nature reviews. Rheumatology Vol. 6; no. 7; pp. 399 - 405
• Main Authors: Yu, David, Tam, Lai-Shan, Gu, Jieruo
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.07.2010; Nature Publishing Group
• Subjects: 692/420/2780; 692/699/1670/2766/1827; Ankylosing spondylitis; Arthritis; Bone Remodeling; Care and treatment; Cytokines; Diagnosis; Disease; Genes; Health aspects; HLA-B27 Antigen - genetics; Humans; Hypotheses; Inflammation; Ligaments; Medicine; Medicine & Public Health; Nonsteroidal anti-inflammatory drugs; Pathogenesis; Pathology; Patients; Physiological aspects; review-article; Rheumatology; Spondylitis, Ankylosing - etiology; Tendons; Tumor necrosis factor-TNF; United States; Los Angeles California; United States > US; China
• ISSN: 1759-4790; 1759-4804
• DOI: 10.1038/nrrheum.2010.79

Numerous hypotheses abound with regards to the mechanisms involved in the pathogenesis of ankylosing spondylitis, which is, at its core, a genetic disease. This Review outlines the main theories and also provides a deeper look at the processes of bone erosion and syndesmophyte formation that are key to disease progression. Ankylosing spondylitis (AS) is a potentially disabling form of seronegative spondyloarthritis. The main symptom of AS is inflammatory spinal pain; with time, some patients develop ankylosis and spinal immobility. The pathology mainly affects the entheses, where ligaments, tendons and capsules are attached to the bone. Three processes are observed at the entheses: inflammation, bone erosion and syndesmophyte (spur) formation. Tumor necrosis factor is an important mediator of the inflammatory processes, but this proinflammatory cytokine is not closely involved in bone erosion or syndesmophyte formation. The major causative factors of AS are genetic, with the gene encoding HLA-B27 being the most important genetic factor. Several other susceptibility genes have also been identified. An enormous number of papers have been published and many diverse hypotheses have been generated regarding the pathogenesis of AS. This Review outlines the key areas of current research in this field, describes several hypotheses regarding the pathogenesis of AS, which are under intense investigation, and concludes with a dissection of the processes involved in bone erosion and syndesmophyte formation. Key Points Ankylosing spondylitis (AS) is a predominantly genetic disease; HLA-B27 is the most important gene Several HLA-B27 -related disease mechanisms are under investigation: the arthritogenic hypothesis, the unfolded protein response hypothesis, and the free heavy chain hypothesis The non- HLA-B27 genes identified so far might have a role in the processing of HLA-B27 molecules or in cytokine regulation In addition to inflammation, bone erosion and syndesmophyte formation lead to patient disability in AS, but these processes appear to be uncoupled from inflammation A major future direction is to understand the processes of bone erosion and syndesmophyte formation in AS, and how these processes can be controlled