Ankylosing Spondylitis
Component
Ankylosing Spondylitis |
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| Antoine Toubert, Chair | |
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Spondyloarthropathies (SA) constitute a group of inflammatory rheumatic diseases including ankylosing spondylitis, reactive arthritis (ReA) or Reiter's syndrome and some clinical forms of psoriatic or inflammatory bowel diseases-associated arthritis. A key feature in SA pathogenesis is the interplay between genetic factors suggested by the familial aggregation of the disease and environmental factors as in the case of ReA cases following outbreaks of Shigella, Yersinia or Salmonella infections. The major predisposing genetic factor which has been identified is the MHC class I molecule HLA-B27 of which at least 13 different subtypes (B*2701 to B*2713) have been described. The direct implication of HLA-B27 in the disease process and the role of triggering bacteria have been documented in the animal models of arthritis. However, despite knowing the tridimensional structure of HLA-B27, its peptide binding rules and the definition of HLA-B27 subtypes, there is still no definitive explanation of the disease mechanism. HLA-B27 is assumed to account for 30%-50% of the total genetic risk. Additionnal genetic factors are certainly important since for instance first-degree relatives of AS patients have an approximately 10-fold higher risk of developing the disease than B27-positive individuals without affected relatives. Genome-wide screenings are currently in progress in several laboratories. Preliminary data indicate candidate markers in chromosomes 2, 6p, 10, 16 and also some evidence for markers within the MHC, especially in the MHC class III region (Brown et al., Arthritis Rheum., 1998, 41: 588). Associations of disease with polymorphism in immune response genes within the MHC (for instance TAP, LMP or MIC genes) have been reported and account for more extensive studies in homogenous groups of patients and ethnically matched controls. This aim will be fulfilled through the worlwide collaboration of clinical centers and tissue typing laboratories in the scope of the 13th IHWC disease component. |
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Antoine Toubert Laboratoire de Biologie Moleculaire Service du Professeur D. Charron Hopital Saint Louis 1 Ave Claude Vellefaux F-75475 Paris, Cedex 10, France Phone: 33-1-42-49-49-49 FAX: 33-1-42-49-48-89 toubert@neptune.chu-stlouis.fr |
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