The pathogenesis of HLA-B 27-related reactive arthritis.

Two major clues are provided to investigators regarding the pathogenesis of reactive arthritis. The first is that the arthritis is induced by infection with certain intracellular bacteria. These include Salmonella typhimurium, Shigella flexneri, Yersinia enterocolitica and Chlamydia trachomatis. The sec ond is that most patients are HLA-B 27 positive. Because the incidence of HLA-B 27 is very high in a related arthritis, ankylosing spondylitis, and also because animals transgenic with the HLA-B 27 gene develop arthritis, it is certain that the HLA-B 27 itself, and not genes in linkage disequilibrium, isthe predisposing factor. Multiple hypotheses are being proposed as to how HLA-B 27 and bacteria jointly induce the arthritis. Although none of them have yet claimed to be the ultimate solution, two major ones have been the subject of most studies. The first is that H LA-B 27 provides the target for a T lymphocyte immune response. The second is that HLA-B27 promotes persistence of the pathogens in the host tissues including the synovia. HLA-B 27 is a major histocompatibility class I protein. Its physiological function is to present peptides to the T cell receptors of CD 8+T lymphocytes. A critical question has been whether in the arthritis patients, there is an immune response against HLA-B 27 complexed with bacteria derived peptides. A positive immune response has indeed been discovered. CD 8+T cell clones have been