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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 {Insert genome suscept. -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.