Although the exact cause of AS is unknown, we do know that genetics play a key role in the disease. Most individuals who have AS also have a gene that produces a “genetic marker,” a protein called HLA-B27. This marker is found in more than 95 percent of people in the Caucasian population with AS. It is important to note, however, that one does not have to be HLA-B27 positive to have AS. Also, a majority of people with this marker never develop ankylosing spondylitis.
Scientists suspect that other genes — along with a triggering environmental factor such as a bacterial infection, for example — are needed to activate AS in susceptible people. HLA-B27 likely accounts for about 30 percent of the overall risk, but there are numerous other genes working in concert with HLA-B27. Researchers have identified more than 60 genes that are associated with AS and related diseases. Among the newer key genes identified are ERAP 1, IL-12, IL-17, and IL-23.
One classic hypothesis has been that AS may start when the defenses of the intestines break down and certain bacteria pass into the bloodstream, triggering changes in the immune response.
The association between ankylosing spondylitis and HLA-B27 varies greatly between ethnic and racial groups.