When you have symptoms of chronic inflammation, pain, and stiffness in certain areas of your body, such as your back, neck, and chest, or the interior portion of your eyes uveitis, especially if you are male and the symptoms began between late teens and your early 30s
A blood sample taken from a vein in your arm
Every nucleated cell in your body has proteins protruding from the cell surface called human leucocyte antigens (HLA). These proteins are very diverse. Several thousand different types are known. Everybody has a number of different types of these proteins on each cell and together they make up an individual’s “Tissue Type”. One common HLA protein is HLA-B27. Its prevalence varies considerably across the world but it is found in about 8% of the UK population.
HLA proteins are of great importance to the human immune system. They enable it to distinguish our own cells and proteins from those of bacteria, viruses and other “invaders” and so enable it to identify these invaders for attack whilst avoiding attacking its own cells.
The test determines the presence or absence of HLA-B27 on the surface of a person's white blood cells (leucocytes). Sometimes a genetic test is used but the test result is essentially the same.
HLA-B27 is found in about 8% of the UK population. Its presence has been associated with several autoimmune disorders. The most common of these disorders is ankylosing spondylitis (AS). In the UK about 95% of people with AS have the HLA-B27 protein expressed on their cells (they are “HLA-B27 positive”). Other disorders that have an association with the presence of HLA-B27 include juvenile rheumatoid arthritis (JRA), reactive arthritis (including Reiter syndrome), and isolated acute anterior uveitis. HLA-B27 is also more common in people with spondylitis associated with inflammatory bowel disease and psoriatic arthritis. HLA-B27 has not been established as a cause of these disorders but HLA-B27 positivity is more common in people with these disorders than in people without them. However, it is important to realise that HLA-B27 is very common and so most people who are HLA-B27 positive do not have any of these disorders.
How is it used?
The HLA-B27 test is primarily requested to help strengthen or confirm a suspected diagnosis of ankylosing spondylitis (AS), reactive arthritis, juvenile rheumatoid arthritis (JRA), or sometimes anterior uveitis . Because HLA-B27 is common, its presence does not prove the presence of the disorder. However, it is helpful as one piece of evidence amongst others like signs, symptoms, and other lab tests to support or rule out the diagnosis of these disorders.
AS is a chronic, progressive condition that occurs more frequently in men than women. Symptoms usually start between the teenage years and early 30's. Often, the initial symptoms are subtle and it is commonly several years before characteristic degenerative changes to bones and joints are visible on X-ray.
- Ankylosing spondylitis is characterised by pain, inflammation, and a gradual stiffening of the spine, neck and chest.
- Reactive arthritis is a group of symptoms that includes inflammation of the joints, urethra, eyes, and skin lesions.
- Juvenile rheumatoid arthritis is a form of arthritis that occurs in children.
- Anterior uveitis is associated with recurring inflammation of the structures of one or both eyes.
The HLA-B27 test may be requested as part of a group of tests used to diagnose and evaluate conditions causing arthritis-like chronic joint pain, stiffness, and inflammation. This group of tests may include an RF (rheumatoid factor) with an ESR (erythrocyte sedimentation rate) and a CRP (C-Reactive protein). HLA-B27 is sometimes used to help evaluate someone with recurrent uveitis that is not caused by a recognisable disease process.
When is it requested?
An HLA-B27 test may be requested when a person has acute or chronic pain and inflammation in the spine, neck, chest, eyes, and/or joints, and the doctor suspects an autoimmune disorder that is associated with the presence of HLA-B27. Doctors frequently must rely on their clinical findings and the HLA-B27 test result when diagnosing ankylosing spondylitis, and other HLA-B27-related disorders, because the characteristic changes to the bones may not be detectable for several years. Under these circumstances, HLA-B27 is not diagnostic but adds additional information, increasing or decreasing the likelihood that the patient has ankylosing spondylitis. An HLA-B27 may also be ordered when someone has recurrent uveitis.
What does the test result mean?
If a person is positive for HLA-B27 and has symptoms such as chronic pain, inflammation, and/ or consequent damage to the spine and joints (as seen on X-ray, or other imaging), then it supports a diagnosis of ankylosing spondylitis, reactive arthritis, or another autoimmune disorder that is associated with the presence of HLA-B27. This is especially true if the person is young, male, and if he experienced his first symptoms before the age of 40.
However, as noted above, HLA-B27 is common in the UK and the vast majority of people who are HLA-B27 positive do not suffer from these disorders. The test result must be interpreted in the context of the clinical symptoms and signs. AS is a slowly developing disorder and the clinical signs of AS may have other causes so it can take some time to establish a diagnosis.
If HLA-B27 is negative, then it is less likely that the symptoms are due to an HLA-B27 associated disorder . However, this does not completely exclude the possibility that the person has the suspected condition, as a small percentage of people with each disorder will be HLA-B27 negative:
- Ankylosing spondylitis: about 95% are HLA-B27 positive, and 5% are negative
- Juvenile rheumatoid arthritis (JRA): about 80% are HLA-B27 positive
- Reactive arthritis: about 60-85% are HLA-B27 positive
- Isolated acute anterior uveitis: about 40-70% are HLA-B27 positive
Whether or not HLA-B27 is positive is genetically determined. HLA-B27 production is controlled by genes, passed from parents to children. If a person has a close family member with an HLA-B27 related disease that affects the joints of the spine (AS or other related condition) and is positive for the HLA-B27 antigen, then that person is at an increased risk of developing a similar disease.
Is there anything else I should know?
Although the diseases associated with HLA-B27 occur more frequently in men, women can also be affected. The signs and symptoms of the diseases associated with HLA-B27 are often milder in women than in men.
With new genetic testing methods, it is now possible to separate HLA-B27 into subtypes. Over 100 different subtypes of the HLA-B27 gene exist. The most common in the U.K. are HLA-B27*05, HLA-B27*04 and HLA B27*02. How the presence of these specific subtypes affects the likelihood of developing an autoimmune disease is not yet known.
What causes the autoimmune disorders associated with HLA-B27?
In most cases, the cause is not known. However, in some cases of reactive arthritis, there is an association between a previous infection by a microorganism, such as Campylobacter, Chlamydia, Salmonella, Ureaplasma, or Yersinia, and the beginning of the disease. HLA proteins are integral to the normal immune response to infections and tow possible mechanisms have been proposed:
- Fragments of self-proteins are bound to HLA-B27 as part of the normal immune process. These may be displayed in such a way that the immune system cannot distinguish them from protein fragments from the microorganisms. An immune response to these “self-proteins” than occurs after the infection has been cleared and so autoimmune disease develops.
- Similarities between the HLA-B27 protein and the proteins found on the surface of the microorganisms have also been found and this similarity may trigger the immune system to fight both the microorganism and the person's own tissues, launching the autoimmune disorder after the resolution of the infection.
Can I be tested for HLA-B27 in my doctor's surgery?
Should everyone have an HLA-B27 test done?
Routine testing of the general public is not recommended. Usually only those with symptoms should be tested. A positive HLA-B27 in a person who does not have symptoms or a family history of HLA-B27-associated disease is not clinically significant or helpful. It is not useful for predicting the likelihood of developing an autoimmune disease.