Arthritis Associated with Mucosal Infections

Infectious agents which are well tolerated by the majority of those infected can give rise to persistent pathology in predisposed individuals. Inflammatory arthritis complicates certain infections of the gastrointestinal and genitourinary tract in a minority of those infected; this is reactive arthritis, which is in turn related to other forms of inflammatory arthritis the spondyloarthropathies (e.g. ankylosing spondylitis) in which host responses to commensal bacteria rather than specific infectious agents may well be important. Reactive arthritis lends itself to clinical investigation, since it is an acute arthritis triggered by known organisms. Thus persistence and distribution of the organism, together with immune responses to it, can be characterised in detail. Since timing of both the triggering infection and the onset of arthritis are well defined, this facilitates studies of the evolution and outcome of disease. A current view of the immunopathogenesis of reactive arthritis highlights several findings: Firstly, although the triggering organism cannot be cultured from affected joints, there is good evidence that bacterial antigens and, in at least some cases, transcriptionally active bacteria, reach the synovium of the inflamed joints. Secondly, vigorous T-cell mediated responses to the triggering organism are readily detected in affected joints; analysis of the bacterial antigens targeted by the immune response can be used to identify differences in patients with arthritis and uncomplicated infection. Lastly, various genetic and environmental factors influence the likelihood of infected individuals developing reactive arthritis, and its severity or persistence. The best known of these is HLA-B27, but additional genes including those that play a role in other spondyloarthropathies are involved. There is now some evidence that these genes may determine the nature of the immune response mounted to the triggering bacterium in reactive arthritis, or to commensal bacteria in other spondyloarthropathies. Lessons gained from the study of reactive arthritis and other spondyloarthropathies may be applied to other diseases associated with infectious agents in which host factors, particularly genes, determine outcome, in contrast to diseases whose course primarily reflects the pathogenic properties of the organism.