title: Genetics of ankylosing spondylitis--insights into pathogenesis.
abstract: Ankylosing spondylitis (AS), an immune-mediated arthritis, is the prototypic member of a group of conditions known as spondyloarthropathies that also includes reactive arthritis, psoriatic arthritis and enteropathic arthritis. Patients with these conditions share a clinical predisposition for spinal and pelvic joint dysfunction, as well as genetic associations, notably with HLA-B(*)27. Spondyloarthropathies are characterized by histopathological inflammation in entheses (regions of high mechanical stress where tendons and ligaments insert into bone) and in the subchondral bone marrow, and by abnormal osteoproliferation at involved sites. The association of AS with HLA-B(*)27, first described >40 years ago, led to hope that the cause of the disease would be rapidly established. However, even though many theories have been advanced to explain how HLA-B(*)27 is involved in AS, no consensus about the answers to this question has been reached, and no successful treatments have yet been developed that target HLA-B27 or its functional pathways. Over the past decade, rapid progress has been made in discovering further genetic associations with AS that have shed new light on the aetiopathogenesis of the disease. Some of these discoveries have driven translational ideas, such as the repurposing of therapeutics targeting the cytokines IL-12 and IL-23 and other factors downstream of this pathway. AS provides an excellent example of how hypothesis-free research can lead to major advances in understanding pathogenesis and to the development of innovative therapeutic strategies.
authors.affiliation: University of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital, Ipswich Road, Woolloongabba, Brisbane, QLD 4102, Australia.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Brown
authors.affiliation: University of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital, Ipswich Road, Woolloongabba, Brisbane, QLD 4102, Australia.
authors.forename: Tony
authors.initials: T
authors.lastname: Kenna
authors.affiliation: NIHR Oxford Musculoskeletal Biomedical Research Unit and Comprehensive Biomedical Research Centre, Nuffield Orthopaedic Centre, Windmill Road, Headington, Oxford OX3 7LD, UK.
authors.forename: B Paul
authors.initials: BP
authors.lastname: Wordsworth
mesh_terms: D000483:Alleles; D015415:Biomarkers / Q000097:blood; D019317:Evidence-Based Medicine; D020022:Genetic Predisposition to Disease; D015796:HLA-B27 Antigen / Q000235:genetics*; D006801:Humans; D018664:Interleukin-12 / Q000235:genetics; D053759:Interleukin-23 / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011237:Predictive Value of Tests; D012307:Risk Factors; D012680:Sensitivity and Specificity; D013167:Spondylitis, Ankylosing / Q000235:genetics* / Q000473:pathology
chemical_list: D015415:Biomarkers; D015796:HLA-B27 Antigen; D053759:Interleukin-23; D018664:Interleukin-12