Reactive arthritis: the role of bacterial antigens in inflammatory arthritis

For more than 100 years it has been suspected that bacteria or products derived from them are deposited in joints and cause arthritis without suppuration. Over this time a vast amount of evidence, much of which is still unchallenged, has accumulated to demonstrate that whole bacteria and subcellular bacterial elements do pass, under certain circumstances, from sites of mucosal colonization or infection into the circulation and thence into joints. Similarly, experimental studies have demonstrated that the deposition of both inert material and bacterial components within synovium is sometimes, but not always, associated with the development and persistence of synovitis. In human reactive arthritis aseptic synovitis follows localized bacterial infection in the gut or genitourinary tract. A genetic predisposition, associated with the HLA B27 antigen, is recognized, and interaction between class I HLA determinants and bacteria-derived antigens may underlie the development of arthritis. Although much remains to be learned about the dissemination of antigens from the primary site of infection in reactive arthritis, strong evidence implicates the deposition of antigenic elements of Chlamydia, Yersinia, Salmonella and perhaps other micro-organisms within the synovium. Immunological findings support the notion that such antigens are being presented within the joint and participating in the induction and/or maintenance of synovitis. It is not yet clear whether such bacteria are complete or viable or whether persistence at an extra-articular site is important to the persistence of arthritis. The possibility that reactive arthritis, and perhaps other forms of seronegative arthritis also, is caused and perpetuated by bacterial antigens within the joint poses new questions about the role of HLA B27 in pathogenesis. It also raises important and exciting issues regarding treatment. Already, studies of antimicrobial therapy have yielded encouraging initial findings, and it is now possible to design and evaluate therapies aimed at blocking specific antigen recognition within the joint.