Enterobacterial Antigens with Tropism for Joint Structures and HLA-B27=Restricted Cytotoxic T-Cells in Reactive Arthritis

Abstract

In reactive arthritis (ReA), sterile synovitis is an immunological sequela following gastrointestinal or urogenital infection with facultatively intracellular bacteria (Yersinia, Salmonella, Shigella, Chlamydia). It is widely accepted now that the development of arthritis is closely related to the persistance of bacteria or bacterial antigens in extraarticular mucosal or lymphoid tissues (i.e. gut mucosa, gut associated lymphoid tissue, genitourinary mucosa); however, it is still unclear which host mechanisms are responsible for the poorer elimination of arthritis-causing microorganisms in those ReA patients. Bacterial components are also camed to the joints where they can be demonstrated in synovial fluid (SF) immune complexes (1) as well as intracellularly in SF phagocytes (2) and synovial membrane cells (3). Although the clinical arthrological picture is very similar in postveneric and postenteric ReA, there seem to be differences in terms of the intraarticular detection of viable bacteria. In postveneric Reiter’s disease, Chlamydial DNA has been detected in synovial membrane specimens using the polymerase chain reaction (PCR) (4). In contrast, Yersinia DNA has been sought in SF cells with negative results so far (5) suggesting that only parts of the Yersinia microorganisms enter the’joint to initiate humoral and cellular immune reactions in Yersinia induced ReA. Our group has focussed attention on the T cellular immune events at the site of synovitic inflammation. We favor the concept of deposition of bacterial components in the synovial compartment of ReA patients. Consecutively, specific recognition of bacterial antigens by synovial T lymphocytes initiates an antibacterial immune response. The immune-mediated inflammation may then be maintained by HLA-B27 restricted, by unspecific or autoreactive immune events even after the bacterial antigens have been cleared. If this hypothesis is correct it will be of interest to study