The Link Between HLA-B27 and Arthritis

By Linda Rath | June 24, 2022

Can you inherit arthritis? This has been a key question for researchers. Now it seems clear that while hundreds of genetic variations are associated with different types of arthritis, they don’t cause disease on their own. Other factors, like smoking, obesity, infection or even childhood trauma are needed to switch the genes on. Plus, some people who have no genetic risk develop arthritis. And plenty of people who carry genes for arthritis never develop it.

HLA Genes

Most genes associated with arthritis belong to a family of genes called the human leukocyte antigen (HLA) complex.  These genes provide instructions for making a protein found on the surface of white blood cells. It helps your immune system tell the difference between your own cells and harmful pathogens like viruses and bacteria. When faulty HLA genes are active, your immune system may not be able to perform this critical job as well as it should.

HLA-B27 and Ankylosing Spondylitis

There are hundreds of HLA genes, each identified by a different number. One gene, HLA-B27, is strongly associated with a big family of rheumatic diseases called spondyloarthropathies. It includes:

• Axial spondyloarthritis
• Axial psoriatic arthritis
• Reactive arthritis

These diseases mainly cause pain, stiffness and inflammation in the spine, hip joints and entheses – places where ligaments and tendons attach to bones. HLA-B27 is also common in people who have inflammatory bowel disease (IBD) or the eye inflammation uveitis. The greatest association, though, is with ankylosing spondylitis (AS), a type of axial spondyloarthritis that attacks the low back and spine.

As many as 90% of white northern Europeans with AS carry the HLA-B27 gene, but this isn’t true of other ethnicities. Black Americans have more severe disease than whites but far fewer carry HLA-B27. Hispanics and Chinese Americans rank somewhere in between. In contrast, HLA-B27 is almost nonexistent in Japan, so Japanese doctors use other markers to help diagnose and monitor AS.

The Role of HLA-B27 in Inflammatory Diseases

How HLA-B27 affects AS and other inflammatory diseases isn’t entirely clear. The prevailing theory – and the one with the most science to back it up – is that the gene changes the makeup of the gut microbiome – the trillions of bacteria, viruses and fungi that reside in the digestive tract. These vast communities of microbes control the immune system, and HLA-B27 may disrupt their finely tuned functioning. It’s known, for example, that people with AS have a less diverse microbiome, with more harmful bacteria compared to helpful ones and a leaky intestinal barrier, which can allow toxins and microbes to escape from gut the into the rest of the body. As evidence: Microbes that should be found only in the gut sometimes show up in the joints of AS patients.

Testing for HLA-B27

No specific test can diagnose AS. Your doctor might test for HLA-B27 if your symptoms, a physical exam and X-rays suggest you have the disease. The gene doesn’t confirm the diagnosis; it simply adds another piece to the diagnostic puzzle. Occasionally, patients are tested to help diagnose juvenile rheumatoid arthritis or, more rarely, uveitis. Still, experts say HLA-B27 testing should generally be reserved for people whose symptoms strongly suggest AS.

Having the gene doesn’t mean you’ll develop AS or a related disease. And if you’ve been diagnosed with AS, having a positive test won’t change your treatment plan. It’s important to note that a recent study linked a positive HLA-B27 test to more severe disease, more bone damage on X-rays and bony growths on the spine that can cause the joints to fuse. Still, it’s hard to square this finding with the prevalence of severe disease among Black Americans. As with other health conditions, barriers to health care and less effective treatments likely play a role.