Remarkable polymorphism of HLA-B27: an ongoing saga.

Histocompatibility antigen HLA-B27 is a normal gene that is distributed worldwide with variable prevalence and shows a remarkable association with ankylosing spondylitis and related spondyloarthropathies. The precise biological explanation for this remarkable association remains elusive. HLA-B27 represents a family of closely related proteins encoded by an ever-increasing number of alleles; there are 75 alleles of HLA-B27 known thus far, based on nucleotide sequence differences, but at the translated protein level, there are 62 known subtypes of HLA-B27. Not all subtypes are disease associated. Moreover, existence of a possible hierarchical ranking among some of the subtypes for their disease association has been observed.

"The Leeds Idea": an historical account of the spondarthritis concept.

In the 1960s, Professor Verna Wright became increasingly interested in possible relationships between certain seronegative "variants of rheumatoid arthritis", as they were then generally known. At the Rheumatism Research Unit, a department within the division of medicine at Leeds University, he gathered around him a succession of research workers, whom he inspired to study aspects of these relationships. The focus was on family studies, as it was thought that genetic factors could be important. The striking association previously noted between sacroiliitis or full-blown ankylosing spondylitis and several of these disorders to be studied - e.g., psoriatic arthritis, ulcerative colitis, and the arthritis associated with Crohn's disease - was to be central for each of these studies. As a provisional collective name for these possibly related conditions, the term "Spondarthritides" was chosen. These were the days before HLA B27, and so the research tools were simply clinical, radiological (for sacroiliitis) and serological (for rheumatoid factor). The research programme confirmed not only links between the primary disorders with ankylosing spondylitis, but also links between the disorders themselves. Over subsequent years, the spondarthritis concept (dubbed by some "The Leeds Idea") has gained further strength from HLA studies internationally. And membership of the group of conditions fulfilling spondarthritis criteria has grown substantially. It is hoped that this now consolidated framework of spondylitis-related entities will pave the way for further research, with exciting prospects of gene-based prevention and/or cure through the increasing sophistication of molecular biology.