title: Mechanisms of Disease: the immunopathogenesis of spondyloarthropathies.
abstract: Research into the pathogenesis of the spondyloarthropathies has examined the role of HLA-B27 and other genes in susceptibility to these diseases. Novel characteristics of HLA-B27 have been discovered, which have allowed hypotheses for an influence of HLA-B27 on disease to be developed that do not reflect its ability to present arthritogenic peptides to CD8(+) T cells. Although a role for CD8(+) T cells has not been excluded, they are not required in the HLA-B27 transgenic rat model, and do not dominate at sites of disease in humans. Studies have also focused on the consequences of the (rather inefficient) intracellular folding of the HLA-B27 heavy chain, the ability of cells to deal with intracellular infection, and their expression of unusual forms of HLA-B27 on cell surfaces (including free heavy chains and dimers). Unusual surface forms of HLA-B27 interact with a different set of receptors from those that recognize conventional class I MHC molecules and thus can be implicated in driving inflammatory responses. Additional candidate susceptibility genes are being identified, either using gene-targeting technology in mice, or genomic screening approaches in humans. In several cases, as with HLA-B27, the evidence suggests that these genes influence the response of the host to bacteria, including pathogens and commensal organisms of the skin and gastrointestinal tract. The concept that spondyloarthropathies are the result of interactions between susceptibility genes, bacteria and the immune system remains a useful model for the pathogenesis of these diseases.
authors.affiliation: Addenbrooke's Hospital, University of Cambridge, Cambridge CB2 2QQ, UK. jshg2@medschl.cam.ac.uk
authors.forename: Hill
authors.initials: H
authors.lastname: Gaston
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018450:Disease Progression; D015796:HLA-B27 Antigen / Q000276:immunology*; D006801:Humans; D025241:Spondylarthritis / Q000276:immunology* / Q000473:pathology
chemical_list: D015796:HLA-B27 Antigen