About our DNA .....

PREVALENCE
The prevalence of HLA-B27 varies between populations— from 50% in Haida Indians to 0/ nil in Australian Aborigines. In the UK general population it is about 8%. HLA-B27 is rare in the American black population whereas Eskimo populations carry it much more frequently than Western Europeans, with prevalence rates of 25% or more. This antigen is associated with ankylosing spondylitis in virtually all racial groups studied. 

PATHOGENESIS
HLA-B27 positive Caucasians have a 20-fold risk of developing any spondylarthropathy, particularly ankylosing spondylitis and undifferentiated spondarthritis.

Family and twin studies of ankylosing spondylitis have shown a polygenic pattern of genetic susceptibility with heritability in excess of 90%. The contribution of HLA-B27 to genetic susceptibility has been estimated to be 20–50% of the total.

Other HLA alleles, most notably HLA-B60 and HLA-DR1, may predispose to ankylosing spondylitis either independently of B27 or in conjunction with it.

MECHANISMS
The main natural function of HLA-B27 is to form a complex with β2microglobulin which can bind short antigenic peptides such as those derived from intracellular microorganisms. Following presentation at the cell surface, the complexes are specifically recognised by cytotoxic lymphocytes which then kill the infected cell.

Viral?/Organisms have been shown to trigger reactive arthritis, including Salmonella, Shigella, Yersinia, Campylobacter, Chlamydia, Mycobacteria and possibly Brucella, all of which habitually survive intracellularly. HLA-B27 appears to enhance the invasion of Salmonella into intestinal epithelial cells.

PREDICTIVE
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-first degree}
Generally, the value of testing for HLA-B27 depends upon the particular clinical situation. Beginning with a clinical estimate of the likelihood of ankylosing spondylitis or a related spondarthropathy.

Seronegative Spondarthritides

Ankylosing spondylitis
Reactive arthritis (Reiter’s syndrome)
Psoriatic arthropathy
Enteropathic arthropathy
Acute anterior uveitis
Juvenile spondarthritis
Undifferentiated spondarthritis
Isolated peripheral enthesitis

ASSOCIATIONS
HLA-B27 and ankylosing spondylitis remains the strongest known relationship between a major histocompatibility complex (MHC) antigen and a disease!

Enthesitis, defined as inflammation of the origin and insertion of ligaments, tendons, aponeuroses, annulus fibrosis and joint capsules, is a hallmark.

The concept of entheseal organ prone to pathological changes in spondyloarthritis is well recognized.

The relevant role of peripheral enthesitis is supported (heel pain or other well-defined enthesopathic pain), axial and peripheral spondyloarthritis.

Episodes of Achilles tendinitis, plantar fasciitis, posterior tibial tendinitis, & dactylitis. Also seen are lateral epicondyle, insertion of the patella tendon into the inferior pole of the patella, femoral quadriceps, and posterior tibial tendons. {continue}Hip disfunct:

Upper lobe fibrosis is the lung condition best known to correlate with HLA-B27.  The antigen may be positively, neutrally or negatively associated with asbestosis. Claims have also been made for an association with other pulmonary diseases, especially pleurisy, pleural abscess, bronchitis and pneumonia and pneumothorax, independently of the presence of ankylosing spondylitis.

Aortic regurgitation occurs in 2–10% of patients with ankylosing spondylitis, and cardiac conduction abnormalities including atrioventricular and intraventricular blocks have been found in one-third of patients with spondylitis.

HLA-B27 related cardiac lesions may be found in the absence of other rheumatological manifestations.
Indeed, an HLA-B27 associated cardiac syndrome comprising severe cardiac conduction system abnormalities and lone aortic regurgitation has been defined, whose link with B27 is almost as strong as that between B27 and ankylosing spondylitis.

Significant association has been reported between HLA-B27 and acute leukaemia, particularly acute myeloid leukaemia.HLA-B27 carriers may have an increased risk of acute leukaemia whilst those with concomitant ankylosing spondylitis may be predisposed to lymphoid malignancies.

While infection with HIV predisposes to spondyloarthropathy,HLA-B27 is the HLA class I molecule most closely associated with non-progression of HIV infection to AIDS.

HLA-B27 can be helpful in a patient complaining of low back pain of an inflammatory character in the absence of radiological signs of sacroiliitis or in patients with an asymmetrical oligoarthritis but without other features of spondarthritis. This has been acknowledged with the inclusion of HLA-B27 positivity as a criterion in the Amor classification criteria for spondyloarthropathy.

Likewise, testing for HLA-B27 can help to differentiate between alternative aetiologies in iritis and aortic regurgitation.

PROGNOSTIC VALUE

Whereas HLA-B27 does not seem to influence the severity of ankylosing spondylitis, in psoriatic spondylarthropathy it may determine not only susceptibility to the condition but also its clinical expression.

It correlates most strongly with isolated axial disease and it may confer some protection against peripheral joint erosions.

Patients with Reiter’s disease and Yersinia andSalmonella triggered reactive arthritis who are HLA-B27 positive have more severe acute disease, more extra-articular features and more frequent chronic back pain and sacro-iliitis.

In C. trachomatis reactive arthritis, more severe or chronic disease could be due to lower concentrations of interferon-γ in the synovial fluid of patients who are HLA-B27 positive than those who are HLA-B27 negative, with consequent impaired clearance of infective agents.

With regard to cardiac disease, the relative risk that a HLA-B27 positive man will need a permanent pacemaker has been calculated to be 6.7 compared with a man who has other B alleles. This association is not, however, present in female patients.

A poor outcome of back surgery has been found in patients possessing HLA-B27.

Atlanto-axial subluxation can occur.

HLA-B27 positive patients with rheumatoid arthritis have about twice the risk of developing subluxation of the cervical spine and an almost threefold risk of subaxial subluxation.

Thus, HLA-B27 may transpire to be a useful prognostic indicator for the later development of instability of the cervical spine and its complications in rheumatoid arthritis.

The discovery of the link between HLA-B27 and a large family of inflammatory rheumatic diseases was one of the seminal advances in rheumatology in the last century. Associations have subsequently been identified with other musculoskeletal and non-rheumatic diseases.

The Test
http://labtestsonline.org/understanding/analytes/hla-b27/tab/test/

The HLA-B27 test is primarily ordered to help strengthen or confirm a suspected diagnosis of ankylosing spondylitis (AS),reactive arthritis, juvenile rheumatoid arthritis (JRA), or sometimes anterioruveitis. The HLA-B27 test is not a definitive test that can be used to diagnose or rule out a disorder. It is one piece of evidence used along with the evaluation of signs,symptoms, and other laboratory tests to support or rule out the diagnosis of certain autoimmune disorders, such as ankylosing spondylitis and reactive arthritis.

Ankylosing spondylitis and reactive arthritis are both chronic, progressive conditions that occur more frequently in men than women. The first symptoms typically occur when a person is in their early 30's. Often, the initial symptoms of these autoimmune disorders are subtle and may take several years before characteristic degenerative changes to bones and joints are visible on X-rays.

Ankylosing spondylitis is characterized 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, and eyes as well as skin lesions.Juvenile rheumatoid arthritis is a form ofarthritis 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 ordered 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 either an ESR (erythrocyte sedimentation rate) or a CRP (C-reactive protein). HLA-B27 is sometimes ordered to help evaluate someone with recurrent uveitis that is not caused by a recognizable disease process.

When is it ordered?

An HLA-B27 test may be ordered when a person has acute or chronic pain andinflammation in the spine, neck, chest, eyes, and/or joints, and the doctor suspects the cause is an autoimmune disorder that is associated with the presence of HLA-B27. An HLA-B27 may also be ordered when someone has recurrent uveitis.

The HLA-B27 test is not diagnostic, but the results add information, increasing or decreasing the likelihood that the person being evaluated has the suspected autoimmune disorder.

Doctors frequently use the HLA-B27 test result when they suspect ankylosing spondylitis but the disease is in an early stage and the vertebrae in the spine have not yet undergone the characteristic changes that would be seen on X-ray.

What does the test result mean?

If a person is positive for HLA-B27 and has symptoms such as chronic pain,inflammation, and/ or degenerative changes to his bones (as seen on X-ray), then it supports a diagnosis of ankylosing spondylitis, reactive arthritis, or anotherautoimmune 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.

If HLA-B27 is negative, then the marker was not detected. This does not mean, however, that the person tested does not have the suspected condition since people who do not have the HLA-B27 antigen can also develop these autoimmune diseases. Likewise, someone who has the HLA-B27 antigen will not necessarily develop one of these conditions. Researchers are trying to determine what factors contribute to the higher likelihood of people with HLA-B27 developing these particular diseases and what actually triggers them.

Whether or not certain HLA antigens will be present is genetically determined. Their production is controlled by genes that are passed from parents to their children. If two members of the same family are HLA-B27 positive and one of them develops a disease associated with HLA-B27, then the other person is at an increased risk of developing a similar disease.

Is there anything else I should know?

Though the diseases associated with HLA-B27 occur more frequently in men, women can also be affected. However, the signs and symptoms related to the diseases can often be milder in women.

With new genetic testing methods, it is now possible to separate HLA-B27 into subtypes. So far, more than 70 different subtypes have been identified, such as HLA B27*05 and HLA B27*02. How the presence of these specific subtypes affects the likelihood of developing an autoimmune disease is not yet known