Ankylosing spondylitis (AS) is the most common form of spondyloarthritis, which is a family of arthritic diseases that affect the spine, sacroiliac joints, and the places where ligaments and tendons attach to bones (called entheses). In AS, inflammation primarily leads to pain and stiffness in the spine and the sacroiliac joints, which join the sacrum (base of the spine) with the pelvis. 

AS has a strong genetic basis, and variations in several genes have been detected that influence the risk of developing this disorder. The strongest link by far is with HLA-B27; certain variations in the HLA-B27 gene are associated with development of AS. Usually HLA genes help your immune system in recognizing and presenting foreign invaders, such as viruses and bacteria, to the immune cells. Here’s what you need to know about HLA-B27.

What is HLA-B27 and how does it affect arthritis?

HLA-B is a gene that provides instructions for making a protein that sits on the surface of cells and helps your immune system determine which proteins it comes in contact with are from your own body and which are foreign and potentially dangerous, such as viruses and bacteria. 

There are hundreds of different forms of the HLA-B gene, designated by numbers. One of them, HLA-B27, is strongly associated with the development of ankylosing spondylitis.

“About 80 to 90 percent of [certain populations of] patients with AS are positive for HLA-B27, and in different populations the prevalence of AS mirrors the prevalence of HLA-B27,” says Abhijeet Danve, MD, assistant professor and director of the spondyloarthritis program at Yale University in New Haven, Connecticut. “How exactly HLA-B27 contributes to the pathogenesis of AS is not entirely clear but extensive work has been done in this regard and several theories have been suggested.”

HLA-B27 is also found in patients with other forms of spondyloarthritis such as psoriatic arthritis, inflammatory bowel disease, reactive arthritis in response to an infection, and isolated acute anterior uveitis (an inflammation of the middle layer of the eye which occurs in some people with autoimmune disorders such as AS), though the association of HLA-B27 with these diseases isn’t as strong as it is with AS.

Should I get a blood test for HLA-B27?

Probably only if your doctor strongly suspects you could have AS, based on a constellation of AS symptoms, or signs of inflammatory back pain.

“We use HLA-B27 as a helpful test rather than a confirmatory test. I send it only in patients with back pain who also have other AS features such as gradual onset of chronic back pain that started before the age of 45, features suggesting inflammatory back pain, a history of heel pain or Achilles tendonitis, uveitis, psoriasis, or a family history of AS, psoriasis, or inflammatory bowel disease,” Dr. Danve says.

Why not just test everyone for HLA-B27? “Because about 7 percent of Americans are positive for HLA-B27 but only 5 to 10 percent of people with a positive HLA-B27 will have AS,” says Dr. Danve. The prevalence of positive HLA-B27 and the risk of developing AS is higher in people with a positive family history of AS, he says.

If you don’t have AS symptoms but are found to be positive for HLA-B27, there’s nothing special that your doctor can do to lessen your chances of developing AS. “There is no data about preventive measures except that you should stop smoking, which is a known risk factor for progression in patients with known AS.”

While HLA-B27 is the genetic variation with the strongest link to AS, there may be tests on the horizon that do a better job at identifying people with the disease. While not yet commercially available, in a recent study from Australia risk scores that took thousands of genetic variations (each with a small impact) into account were better able to identify people with AS than HLA-B27 alone.

Can you have AS without being positive for HLA-B27?

Yes. While, in general, populations with higher levels of HLA-B27 have higher rates of AS, the connection between HLA-B27 and AS isn’t the same in all ethnic groups. For example, a 2017 study published in Clinical Rheumatology found that black Americans had more severe symptoms than white patients but only 63 percent were positive for HLA-B27 (compared with 85 percent of white patients and 87 percent of Latinos).

People diagnosed at an early stage of AS, called non-radiographic axial spondyloarthritis, are also less likely to have HLA-B27, with just 50 to 75 percent of people testing positive, according to Dr. Danve.

Will being positive for HLA-B27 change my treatment or the likely course of my disease?

Your treatment is unlikely to change, but there are several ways that AS seems to differ in those who are HLA-B27 positive.

“Patients with a positive HLA-B27 develop AS earlier, are diagnosed earlier, and are more likely to have a positive family history. Compared with other people who have AS, they are more likely to develop uveitis and less likely to have psoriasis or inflammatory bowel disease,” Dr. Danve says. 

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