HLA-B27 Negative: The Other Genetic Markers
People with axial spondyloarthritis (AxSpA) may be familiar with the HLA-B27 gene and its connection to a positive diagnosis. About 90 percent of people with radiographic AxSpA (also called ankylosing spondylitis) test positive for the HLA-B27 gene. It can be frustrating if you have AxSpA and do not have the HLA-B27 gene. Not having HLA-B27 may cause a delay in diagnosis. A delay in diagnosis could mean a delay in effective treatments, which may lead to spinal fusion.1
However, the National Institutes of Health (NIH) recognizes there are other genetic markers associated with AxSpA. While these genes may interact with the HLA-B27 gene, they are considered to be markers of the condition on their own.2
The ERAP1 genetic marker
The full name for the ERAP1 gene is endoplasmic reticulum aminopeptidase.1 This gene may also be referred to as ARTS1. This gene is responsible for cutting proteins on the surface of cells into smaller portions. These portions are called peptides. The ERAP1 gene specifically cuts peptides called cytokine receptors. Cytokines are important in triggering inflammation. When ERAP1 cuts the cytokine receptors, they cannot signal to the cell. This can play a part in inflammation.1,2
ERAP1 also cuts proteins that signal immune responses. Sometimes ERAP1 cuts these proteins into peptides incorrectly. When the proteins reach the cell surface, they can trigger an immune response. Since the peptides are not correct, the body no longer recognizes the cell, which causes it to break down.2
Doctors are not sure how ERAP1 specifically affects AxSpA. There may be other factors that could cause ERAP1 to increase a person’s risk for axial spondyloarthritis. These factors could be the environment or other genes we do not currently know enough about.2
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The IL1A genetic marker
The full name for the IL1A gene is interleukin-1 alpha. The IL1A gene is responsible for making a protein known as interleukin-1 alpha. This protein is part of a larger group of proteins known as interleukins. These proteins are part of the immune cells. IL1A stimulates the immune system and the inflammatory response. It is part of the system that recognizes when there are bacteria and viruses in your body.2
Doctors do not completely understand how the IL1A gene effects AS. They know that there are a few different types of IL1A genes and that some of these increase your risk of AxSpA.2
IL1A is a long chain of proteins. Each IL1A gene changes just 1 building block in that chain of proteins. Doctors believe that part of the chain is changed to make the body cause inflammation. There may also be other genes or environmental factors that may change IL1A. IL1A can also be a factor in other conditions besides AS.2
The L23R genetic maker
The full name for the IL23R gene is interleukin-23 receptor. The IL23R gene is responsible for making interleukin 23. IL23 is also a protein that is part of the immune system and helps the body recognize bacteria, viruses, and other diseases. IL23R causes a cell to respond to the immune system. It causes inflammation, which is one of the ways the body fights off infections. This is much like getting a fever when you are sick.2,3
Like IL1A, IL23 is a long protein strand. The IL23R genes may rearrange many of the building blocks of this strand. Some of these changes are responsible for AS. Like IL1A, IL23R also may lead to other immune disorders, including psoriatic arthritis, ulcerative colitis, and Crohn’s disease. While doctors knew that IL23R was responsible for other diseases, they have only started to understand how it affects AxSpA.2,3
Things to consider when you're HLA-B27 negative with ankylosing spondylitis
It is important to note that genetics research is constantly making new discoveries. While doctors currently know that some specific genes are connected to an AxSpA diagnosis, there may be other genes that researchers do not know about yet. Do not get discouraged if your AS diagnosis is not tied to HLA-B27. Doctors and researchers are working to better understand AxSpA. Your genetic link may be right around the corner.
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