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Despite an extensive amount of research that has been conducted over the past few decades, the exact cause of ankylosing spondylitis (AS) remains unknown. Investigators are puzzled by the insidious onset that leads to diagnosis only after several years. The pathogenesis appears to be related to a complex interaction of immunological, genetic, and environmental factors which are not yet clearly understood. Scientists, however, have identified certain risk factors that may increase a person's chances of developing ankylosing spondylitis.

Risk factors for ankylosing spondylitis include:

• Genetic predisposition
• Inflammatory bowel disease
• Immune response mediators
• Male gender

Genetic Predisposition

Ankylosing spondylitis tends to run in families. Evidence for a possible genetic predisposition to AS is supported by the findings that a specific Human Leukocyte Antigen (HLA) tissue type known as HLA-B27 occurs in approximately 90-95% of individuals with AS. In contrast, the HLA-B27 genetic marker is only found in about 6% of the overall general population. This suggests that individuals with the HLA-B27 tissue type may be more genetically predisposed to developing AS than people who do not possess the HLA-B27 genetic marker. The presence of the HLA-B27 marker is considered to account for 20-40% of the overall risk of developing AS.

Most people with the HLA-B27 marker do not develop AS nor does the HLA-B27 marker need to be present in order to develop AS. It is estimated that less than 2% of individuals with the HLA-B27 gene in the general population develop AS. The HLA-B27 gene does not cause AS but seems to make people more susceptible to the condition.

Ankylosing spondylitis is 10 to 20 times more common among individuals with a first-degree relative (parent or sibling) who has AS than in the general population. If one parent is positive for the HLA-B27 gene, there is a 50% chance that they will pass-on this gene to their offspring. The likelihood of the child developing ankylosing spondylitis, however, is less than 10%.

Inflammatory Bowel Disease

There is some evidence that bacterial infections may "trigger" the underlying chronic inflammation that leads to the development of ankylosing spondylitis. The association between ankylosing spondylitis and inflammatory bowel diseases (Crohn's disease and ulcerative colitis) suggests that an exaggerated immune response to bacteria in the gastrointestinal tract may be involved in the underlying pathogenesis of AS. Ankylosing spondylitis may develop when host defenses in the intestine break down and bacteria from the intestines travel through the bloodstream into the region of the sacroiliac joint and trigger a chronic inflammatory response.

Immune Response Mediators

Ankylosing spondylitis may be related to secretion of cytokines (immune response mediators) such as TNF-alpha as a result of prolonged immune response to infection. Studies have suggested a role for TNF-alpha in the pathogenesis of ankylosing spondylitis based on the following observations:

• Elevated levels of TNF-alpha in the sacroiliac joints of patients with AS
• Elevated levels of TNF-alpha in certain joints of patients with psoriatic arthritis which is one type of spondyloarthropathy