U.C.L.A. Rheumatology Pathophysiology of Disease Course Lecture,
Second Year Medical School 1997

  
 
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Ankylosing Spondylitis     Page 18
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Ankylosing Spondylitis
written by:
Peng Thim Fan, M.D.
graphics by:
Craig Wiesenhutter, M.D.
       This disease belongs to a group of arthritic conditions called the "seronegative spondyloarthropathies". It includes AS, Reiter's Syndrome, psoriatic arthritis, and the arthritis associated with inflammatory bowel disease. The term "seronegative" refers to the absence of rheumatoid factor in the serum of such patients. "Spondyl-" is Latin for spinal involvement. Unlike RA, the axial skeleton is a primary target of the inflammatory process in this group of diseases. "Arthropathy" refers to peripheral joint disease which is a secondary target in this group. Unlike SLE and RA, AS was previously thought to be more prevalent in men. Closer study suggests that the disease is equally frequent in men and women but for unknown reasons the disease expression is much milder in women so that more of the advanced clinical features are seen in men.
       The disease is strongly associated with the Class I antigen, HLA-B27. This antigen is found in 6% of the general Caucasian population but it is seen in 90% of patients with AS. It is also strongly associated with Reiter's Syndrome (80%), another seronegative spondyloarthropathy. The inheritance of the HLA-B27 antigen confers a 20% risk for the development of either AS or Reiter's Syndrome. Following a gastrointestinal infection caused by Salmonella, Shigella, Campylobacter, or Yersinia, or nonspecific urethritis caused by Chlamydia trachomatis, a HLA-B27 positive person may develop Reiter's Syndrome. The arthritis which occurs is not caused by the bacterium growing in the joint but rather by a reactive inflammatory process directed at bacterial antigens which is probably immunologically mediated. It is currently thought that a different and as yet undefined environmental agent may trigger the onset of AS in the susceptible B27-positive individual. One of the most intriguing areas of study is the relationship between the HLA-B27 antigen and the known bacterial agents that can provoke Reiter's Syndrome. The biological function of the HLA-B27 antigen is to present antigenic peptides to CD8+ T lymphocytes. These are cytotoxic T-lymphocytes that are capable of directly killing target cells through direct cell contact via the T-cell receptor. It is possible that certain "arthritogenic" bacterial 		   
 
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