No abstract

Thirty years after its discovery, 1,2 the association between HLA-B27 and ankylosing spondylitis remains the strongest known relationship between a major histocompatibility complex (MHC) antigen and a disease. Epidemiological studies in the 1960s and early 1970s identified close links between several distinct forms of arthritis that were given the collective title of the seronegative spondarthritides. 3 Recognition that HLA-B27 was a genetic marker for these diseases led to a review of the composition of the group, resulting in the exclusion of Whipple's disease and Behçet's syndrome and the inclusion of other conditions such as undifferentiated and formes frustes of spondarthritis 4 and HLA-B27 associated isolated peripheral enthesitis. 5 Notwithstanding a 28-44% prevalence of HLA-B27 in affected patients, Whipple's disease was excluded after being found to be caused by the actinobacterium Tropheryma whipplei, 6 whilst Behçet's syndrome forfeited its place for many reasons including a lack of association with HLA-B27. 7 Box 1 lists the seronegative spondarthritides currently recognized-now more commonly known as the seronegative spondylarthropathies or spondyloarthropathies.

The HLA-B27 molecule is one of the most fascinating in medicine. Its contribution to the aetiopathogenesis of SpA and other diseases, and its protective action in certain infections, continue to challenge our understanding of its immunobiology and physiological roles. Animal studies have helped to cast light on ways in which HLA-B27 exerts its effects. Subtle variations in structure and behaviour between B27 subtypes that are strongly associated with SpA, compared with those whose association is neutral or weak, are helping to elucidate its pathogenetic mechanisms. However, none of the current hypotheses fully explains the observed actions of HLA-B27. Consequently, attention is turning to how haplotype linkages and genetic networks involving other MHC and non-MHC genes influence the penetrance and clinical expression of B27. HLA-B27 gives an intriguing insight into the connection between heredity and disease. As well as its close links with SpA, various other associations have been reported between B27 and diseases of different organs and systems. Evidence is also accumulating that it mitigates the virulence of HIV and other viral infections. The role of HLA-B27 as an aid to diagnosis, prognosis and disease management is gradually becoming clearer.

No abstract

Oesophageal dysfunction can occur in a variety of musculoskeletal conditions, most notably the autoimmune connective tissue diseases. However, correlation between oesophageal symptoms and investigations is frequently poor. It is often uncertain whether symptoms are caused by the underlying disease or by its treatment. As the primary disease process may not be responsive to treatment, correctable iatrogenic causes should always be sought.