• E Toussirot and D Wendling.
• Service de rhumatologie, CHU Jean-Minjoz, boulevard Fleming, 25030 Besançon cedex, France. eric.toussirot@ufc.univ-fcomte.fr
• Rev Med Interne. 2006 Oct 1; 27 (10): 762-71.

BackgroundAnkylosing spondylitis (AS) is an inflammatory rheumatic disease with axial involvement but its physiopathology remains unexplained. This latter combines genetic and environmental factors as well as an abnormal immune response.Current Topics And Important ResultThis review addresses the different aspects of AS immunogenetic. A genetic background in AS is suggested by familial cases, concordance rate in twins and transmission of the disease in siblings. Ankylosing spondylitis is strongly associated with the expression of the HLA Class I antigen, B27, but also with other genes not yet identified since currently, only chromosomic area have been linked to AS. Studies of candidate genes or genome screening allow to determine these chromosomic regions. HLA-B27 is directly associated with the disease physiopathology as suggested by animal models of rats transgenic for human HLA-B27 and beta2 microglobulin. This HLA molecule have original biological properties, in particular a slow heavy chain folding and the formation of heavy chain homodimers without light chain. However, HLA B27 is a functional molecule and assumes its property of presenting peptide of 9 amino acids to CD8+ T cells. Interaction modelling studies between HLA B27 and peptides have identified peptide and peptide groove amino acid sequences, with the identification of critical positions on the HLA B27 molecule for the peptide interaction. Original biochemical properties of HLA-B27 include diminished bacterial antigen response and CD4+ T lymphocyte stimulation. Innate immunity is also of interest in AS, as suggested by the presence of macrophage and polymorphonuclear neutrophils in AS synovitis, as well as the contribution of Toll-like receptors.Future Prospects And ProjectsThus in AS, the inflammatory process and then the clinical consequences may be explained by the involvement of HLA-B27, a bacterial antigen presentation, an abnormal immune response and the contribution of innate immunity, T CD4+ but also T CD8+ cells. The original molecular structures of HLA-B27 are certainly involved in this complex physiopathology, but their direct influence on the disease remains to be precised.

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