Role of HLA-B27 in Spondyloarthropathies

Abstract

HLA-B27 associated spondyloarthropathies are a group of inflammatory diseases primarily affecting the spine and peripheral joints. Ankylosing spondylitis (AS) is a prototypic disorder of spondyloarthropathies. Approximately 0.1 % of the Caucasian population suffers from AS in North America. Some 90% of patients with this disorder carry the HLA-B27 gene, which is present in 8% of the Caucasian population (Gran and Husby 1994). There are nine subtypes of HLA-B27 (B*2701 to B*2709), differing from each other by a few amino acid residues (Khan 1994). Sequence analysis of α1, α2 and α3 domains of HLA-B27 from a patient and a normal individual did not show any differences (Coppin and Mcdevitt 1986). This suggests that other genetic and/or environmental factors besides HLA-B27 are required for disease susceptibility/pathogenesis. Enterobacteria including Klebsiella pneumoniae, Shigella flexneri, Salmonella typhimurium, Yersinia enterocolita and Chlamydia trachomatis have been isolated from patients with spondyloarthropathies and are potential triggers because of the temporal relationship between infection and disease onset or reactivation. Some bacterial proteins (from Klebsiella, Yersinia, etc.) have amino acid sequences that mimic HLA-B27, which may initiate breakdown of tolerance to self-antigens or allow autoimmune responses to develop in these patients. In order to understand the mechanism(s) involved in pathogenesis and the role of HLA-B27 in this disease, several laboratories generated HLA-B27 transgenic mice and rats. HLA-B27 transgenic mice were either asymptomatic or developed mild disease (IVANYI ET AL. 1991). Our studies showed increased pathogenicity of Yersinia enterocolitica 0:8\NA in HLA- B27 transgenic mice (NICKERSON et al. 1990a). HAMMER et al. (1990), using HLA-B27 transgenic rats, observed spontaneous inflammatory disease. Recent studies have given us new insights into the structure and function of HLA-B27 molecule and its subtypes. These observations should set the stage for understanding the role of this gene and that of bacteria in the pathogenesis of these diseases.KeywordsAnkylose SpondylitisMolecular MimicryReactive ArthritisYersinia EnterocoliticaDouble Transgenic AnimalThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.