The association between HLA-B27 and ankylosing spondylitis could be explained by a theory of crossed tolerance, which proposes that Gram negative bacteria have antigens similar to HLA-B27. Experimental studies with human sera with anti-HLA specificity and rabbit sera with anti-Klebsiella specificity demonstrate a partial crossed reactivity between HLA-B27 and Klebsiella. Clinical studies have shown that Klebsiella can be isolated from patients with ankylosing spondylitis during relapses or active phases of the disease. The theory of crossed tolerance proposes that ankylosing spondylitis is a reactive arthritis which develops after infection with Gram negative bacteria. The agent directly involved in causing the disease is an anti-bacterial antibody which binds to self antigens with partial crossed reactivity, such as HLA-B27, and the inflammation develops as a result of triggering of the complement cascade by the antigen-antibody complex.