Ankylosing spondylitis (AS) is a type of inflammatory arthritis. It mainly affects the spine and the joints that connect the spine to the pelvis. People with AS may also develop inflammation in other joints, the eyes, the skin, the lungs, the gut, or the heart.
AS affects about 32 out of 10,000 people in North America, according to estimates reported in 2014. This type of arthritis is more common in people of European descent, though it also affects others.
AS has a strong genetic component and tends to run in families. Anyone with a first-degree relative who has AS is much more likely than average to develop the disease.
Ongoing research into the genetic aspect of AS may help scientists develop more effective strategies for diagnosing and treating it.
AS is an autoimmune condition. The immune system attacks healthy tissues, which leads to inflammation and tissue damage.
Experts have not identified any single cause of AS. Instead, it seems to arise through complex interactions between genetic and environmental factors.
The HLA-B27 gene is most strongly associated with the development of AS. However, other genes may also increase the risk of developing this disease.
According to a review published in Nature Reviews Rheumatology, genome-wide association studies have identified more than 100 genes and regions between genes that are associated with AS.
HLA-B27
The HLA-B gene provides instructions to the body for making HLA-B protein. This protein helps the immune system distinguish between foreign microbes and the body’s own cells.
The HLA-B gene has hundreds of variants. One of them is HLA-B27. People who carry certain subtypes of HLA-B27 have an increased risk of developing AS.
HLA-B27 is more common in some groups than others. “It’s more predominant in Western and Northern Europeans,” Dr. Brett Smith, a rheumatologist at the Blount Memorial Physicians Group, in Alcoa, Tennessee, explained to Medical News Today.
Research from 2020 suggests that among people of European descent, about 85% of those with AS are positive for the HLA-B27 gene. By comparison, only 8% of people without AS carry this gene.
Although HLA-B27 increases the risk of AS, most people with this genetic variant never develop the disease. Only about 6% of HLA-B27-positive people develop AS, the researchers report.
Other genes
The HLA-B27 gene accounts for about 20% of the overall heritability, or genetic component, of AS. Many other genes may also play a role.
For example, certain variants of the ERAP1 gene appear to further increase the risk of developing AS in people who are HLA-B27-positive.
Scientists have also linked multiple genetic variants involved in the immune system’s interleukin (IL)-23 and IL-17 pathway to AS. These genes code for proteins that help guide the body’s immune responses.
More research is needed to understand the role that different genes play in the development of AS. Additional research is also needed to understand how genetic and environmental factors interact to cause this disease.
There is wide variability in how AS affects people. Some people with AS experience mild symptoms, while others develop more severe symptoms and complications over time.
Evidence suggests that certain genetic factors may affect how the disease progresses. An older study, published in 2001, found that disease activity and ability to function were both closely related to genetics in people with AS.
In recent years, scientists have sought to identify specific genes that may affect disease progression in AS.
For example, one 2015 study linked two variants of the RANK gene to increased spinal damage in AS. This gene plays a role in immune function and bone repair.
Researchers have also linked some genetic variants associated with AS to other autoimmune conditions.
For instance, people with AS who are HLA-B27-positive are more likely than those without the gene to develop acute anterior uveitis, a type of eye inflammation that can cause:
- eye pain and redness
- light sensitivity
- blurred vision
If a healthcare provider thinks that a person might have AS, they may order a blood test to check for the HLA-B27 gene. However, the results of this test alone are not enough to diagnose AS.
“It is used, but it’s only one part of the criteria [for AS diagnosis],” Dr. Smith confirmed.
If someone tests positive for HLA-B27, it does not necessarily mean that they have or will develop AS. Most people who carry this genetic variant never develop the disease.
If someone tests negative for HLA-B27, their chances of having AS are lower. However, a small proportion of people with AS do not carry this gene.
To make a diagnosis, healthcare professionals also take into account the person’s symptoms and findings based on imaging tests and a musculoskeletal examination.
For example, they may check for signs of the disease using X-rays or MRI scans. They may also conduct blood tests to check for signs of inflammation.
There is no known cure for AS. However, treatments can help relieve symptoms, improve physical function, and reduce the risk of certain complications.
The American College of Rheumatology, Spondylitis Association of America, and Spondyloarthritis Research and Treatment Network
If physical therapy and NSAIDs alone are not enough, these organizations recommend treatment with a type of biologic medication known as a tumor necrosis factor inhibitor (TNFi).
If a TNFi is not effective or suitable, a healthcare professional may prescribe another type of biologic, a Janus kinase inhibitor, which is sometimes called a JAK inhibitor, or other medications.
Ongoing genetic research may help scientists develop new treatment strategies for AS. It may also help experts learn which treatments are most likely to benefit different people.
“If we know which genetic loci somebody’s disease mechanism is driven by, we might be able to choose a more appropriate targeted treatment,” Dr. Smith explained, adding, “It’s almost like the ability to use a bow and arrow and try to hit the bull’s eye.”
Although the exact cause of AS is still unknown, genetics and environmental factors appear to play a role. Multiple genetic variants, including HLA-B27, have been linked to the disease.
Genetic research may help scientists develop new diagnostic tests and treatments for AS. It may also help them target treatments for different people more effectively.