What Are Causes and Risk Factors For AS?

Reviewed by: HU Medical Review Board | Last reviewed: February 2019 | Last updated: August 2020

While the exact causes of ankylosing spondylitis (AS) aren't fully understood, researchers have found some pieces of the puzzle. In addition, there are several risk factors that have been identified.

What's the difference between a cause and a risk factor?

Disease causes are not the same as risk factors. "Causes" directly contribute to the development of a disease. "Risk factors" may play a part in a disease but having one or a few does not mean you will automatically get it.

What causes ankylosing spondylitis?

What exactly causes AS to develop in the body is generally unknown, although experts believe it is a combination of genetic, environmental, and factors related to the immune system.

Genetic causes

Genetics includes traits passed down from parents to children (inherited) as well as mutations that can occur in the body over time (acquired). One genetic marker that has been identified as playing a role in the cause of AS is called HLA-B27. It is estimated that 90-95% of Caucasians with AS are HLA-B27 positive.2,3 However, not everyone with the HLA-B27 mutation develops AS, and it is believed that many people in the general population have the HLA-B27 marker but will not develop the condition.3 In addition, some people with AS do not have the HLA-B27 marker. The association between the presence of HLA-B27 and AS varies greatly among different ethnic groups, with the highest rate of HLA-B27 occurring in Caucasians.2

There have been more than 60 other genetic factors that have been identified as playing some role in the cause of AS. Variations in several additional genes, including ERAP1, IL1A, and IL23R, have also been associated with ankylosing spondylitis. Researchers have also identified a strong genetic connection between AS and inflammatory bowel disease (IBD), and the two conditions often commonly run in families. Genes that are associated with both AS and IBD include STAT3, IL-23, and IL-12B, although how these genes influence each condition aren't clear.4

Environmental and immunologic causes

While genetic causes play some role, researchers know that additional factors from the environment combine with genetic factors in the development of AS. Some environmental factors seem to turn on certain mechanisms in the immune system, causing a change in how the immune system functions.2

Changes in the microbiome are also believed to play a role in how AS develops. The microbiome is the collection of different microorganisms, like bacteria, fungi, and viruses, that are naturally a part of the human body. The microbiome plays many important roles, including the function of the immune system. Changes in the microbiome can lead to dysfunction in the immune system and have been linked to several autoimmune diseases.4 Many research studies have found that people with AS have an increased incidence of Klebsiella pneumoniae, a bacteria commonly found in the gut. In the gut, Klebsiella does not cause infections, but if it gets into other parts of the body (like the respiratory system), it can cause infections.4-6

Risk factors of ankylosing spondylitis

Characteristics that have been identified as increasing a person's risk of developing AS include:

  • Biological Sex: Men are more likely to develop AS than women, and it is estimated that it occurs in 2-3 men for every woman with AS.2,7
  • Age: AS most often occurs in teens or younger adults, under the age of 45. Approximately 10-20% of people with AS begin having symptoms before age 16. Most begin to have symptoms between the ages of 20 and 30.2,7
  • HLA-B27 marker: Testing positive for the HLA-B27 marker increases a person's risk of developing AS, although some people with the marker do not develop the condition.2
  • Family history: Having a family history of AS increases a person's risk of developing it.2
  • Gastrointestinal (GI) infections: Frequent GI infections have been associated with an increased risk of developing AS.2
  • Smoking: Smoking is a major environmental risk factor. It also worsens the severity of the disease. Studies have shown that it can double the risk for spinal damage.

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