Causes and Risk Factors

Reviewed by: HU Medical Review Board | Last reviewed: September 2022

The exact causes of axial spondyloarthritis (axSpA) and its subtype ankylosing spondylitis (AS) are not fully understood. But researchers have identified several risk factors for these conditions. Research is ongoing, and pieces of the puzzle are starting to come together.1

Causes of axial spondyloarthritis

The exact causes of axSpA are unknown. But researchers believe that a combination of genes, the environment, and other factors may play a role in triggering the disease.1

Risk factors for axial spondyloarthritis

Risk factors put people at risk of possibly developing a disease. If you have one or more risk factors for a disease, you are more likely but not certain to develop it. For example, people who smoke are at a higher risk of getting lung cancer, but not everyone who smokes gets lung cancer.2

Risk factors for axSpA involve:1-7

  • Genes and genetic markers
  • Environmental conditions and behaviors
  • Intestinal health
  • Age
  • Biological sex


Some genes may increase the risk that a person will develop axSpA. A person is more likely to develop axSpA if a family member has one of these genes or genetic markers.1,3

People who have a genetic marker called HLA-B27 are at a higher risk of developing axSpA. But not everyone with this marker will develop axSpA, and many people with axSpA do not have this marker. This suggests that other factors must also be involved in the development of the condition.1,3

Researchers are studying the role of genes in axSpA so they can better understand how it develops and find new ways to treat it in the future.1,3

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The interactions between a person's genes and their environment play a role in causing axSpA. In other words, a person may be more likely to develop axSpA if they have a certain gene, but they will develop the condition only if they are exposed to the right environmental factors.3,4

Some environmental factors seem to affect certain parts of the immune system, which changes how it functions. This means things in the environment could potentially trigger the disease. Things like smoking, infections, and even changes in a person's gut bacteria can contribute to the development of axSpA.3,4

Smoking is a particularly bad environmental risk factor for axSpA. Not only does it increase a person's risk of developing the disease in the first place, but it also worsens existing cases and speeds up disease progression.1

While you cannot change your genes, you can try to avoid exposure to things in your environment that might trigger the disease. If you are already living with axSpA, take steps to reduce your exposure to potential triggers. For example, take steps to quit smoking. This will help you manage your symptoms and prevent further damage to your joints.3,4

Gut microbiome

Your gut microbiome is made up of the trillions of good and bad bacteria that live in your gastrointestinal tract. The mix of bacteria in your gut microbiome can affect your risk of developing certain diseases, including axSpA.5

Researchers believe that the gut microbiome may play a role in axSpA by affecting the way the body reacts to inflammation. Some studies have found that people with axSpA are more likely to have less diversity of good bacteria in their gut microbiome. This suggests that the gut microbiome may play a role in the development of axSpA. However, more research is needed to confirm this link.5

Some research has found that people with AS have more Klebsiella pneumoniae, a bacteria commonly found in the gut. Klebsiella is not harmful when it is in the gut. But if it enters other parts of the body, it can cause infections. These findings are weak and need more evidence to support them.5


In 92 percent of cases, AxSpa begins in adults under age 45. Most people start to have symptoms between the ages of 20 and 30. People who have the HLA-B27 genetic marker tend to develop symptoms earlier than those who do not.1,3,7

Biological sex

Historically, axSpA has been reported in many more men than women. But recent studies show that women have a different axSpA disease course than men. The kind of damage that can be seen on X-rays is more likely to occur in men than in women. This may lead to women being diagnosed less often despite being affected at the same rate.6

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