Role of enterobacteria and HLA-B27 in spondyloarthropathies: studies with transgenic mice

Several MHC (major histocompatibility complex) genes are associated with increased incidence of disease. The strongest association is between the class I gene, HLA-B27, and ankylosing spondylitis (AS). HLA-B27 is also highly associated with Reiter's syndrome. As not all subjects with HLA-B27 develop AS or Reiter's syndrome, environmental factors may have a key role in the pathogenesis of these arthritic diseases. Several studies have implicated klebsiella in the development of AS, whereas Reiter's syndrome may result from infection with yersinia, shigella, salmonella, campylobacter, or chlamydia. Transgenic mice present a unique opportunity to study the association of specific MHC genes and disease. HLA-B27 transgenic mice were produced to study the association of HLA-B27, bacterial infection, and arthritic disease. Mice with the HLA-B27 gene are more susceptible to intravenous infection with Yersinia enterocolitica 0:8 WA than negative litter mates as shown by a higher incidence of spinal abscesses and mortality. Understanding the mechanism(s) responsible for this difference may yield valuable insights into the pathogenesis of HLA-B27 associated disease in humans.