HLA-B27

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.

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.

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.

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.

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.