SP0016 The spondyloarthropathies as a paradigm for the induction of an autoimmune response by bacteria

Abstract

The spondyloarthropathies (SpA) comprise ankylosing spondylitis (AS), reactive arthritis (ReA) or Reiter’s syndrome, arthritis/spondylitis with inflammatory bowel disease (IBD) and arthritis/spondylitis with psoriasis. The main link between each other is the association with HLA-B27, the same pattern of peripheral joint involvement with an asymmetrical arthritis predominantly of the lower limbs, and the possible occurrence of sacroiliitis, spondylitis, enthesitis and uveitis. Bacteria play a central role in the pathogenesis of the SpA. This is most obvious in ReA which is triggered by preceding bacterial infections of the urogenital or gastroenteral tract. In arthritis/spondylitis associated with IBD a causative role of gut bacteria is also assumed which can stimulate the cellular immune sytem because the breakage of the gut barrier. Because between 20–50% of HLA-B27-positive patients with ReA or IBD move on to AS a causative or triggering role of bacteria can also be assumed in AS. Due to more recent studies using new imaging techniques such as MRI and immunohistological investigations it can now be assumed that the immunopathology of SpA occurs typically at the interphase of bone and cartilage and that synovitis is only a secondary event. Although at the moment it cannot be excluded that bacteria or pieces of bacteria persist in these structures this seems to be unlikely. Thus, an autoimmune response triggered by a bacterial infection seems to be more likely. Cartilage derived proteins such as aggrecan could be, according to studies in animal models of SpA and to studies in SpA patients, a primary target of this autoimmune response. Such a response could be due to cross-reactivity with a bacterial antigen. This possible course of events leading to a chronic immune response in SpA has to be proven in the near future. The identification of target antigens would offer the possibility to switch off the antigen-specific immune response as a new exciting treatment option.