HLA-DRB1 alleles encoding the shared epitope associated with rheumatoid arthritis confer additional susceptibility to seronegative spondyloarthropathies in HLA-B27-positive Japanese individuals

Although the crucial role of HLA-B27 for the development of seronegative spondy-loarthropathies (SpA) has been established, family and twin studies indicated the presence of additional genetic factors. To determine whether HLA-DRB1 gene acts as an additional susceptibility factor for SpA in HLA-B27-positive Japanese individuals, complete HLA-DRB1 allele typing of 23 HLA-B27-positive patients (21 with ankylosing spondylitis, one with Reiter’s syndrome, and one with uveitis and sacroiliitis) and 17 HLA-B27-positive healthy individuals was performed using polymerase chain reaction-microtiter plate hybridization (PCR-MPH) assay. Twenty-two of patients’ 46 HLA-DRB1 alleles (47.8%) were those that encode the shared epitope associated with rheumatoid arthritis, as compared with eight of 34 DRB1 alleles of healthy HLA-B27-positive individuals (23.5%). This difference was statistically significant [odds ratio (OR)=2.98.P=0.036]. Seventeen of 23 patients were positive for one or two alleles coding for the shared epitope, as compared with seven of 17 healthy individuals (73.9 versus 41.2%, OR=4.04,P=0.053). These results suggest that HLA-DRB1 alleles encoding the shared epitope may act as an additional susceptibility factor for the development of SpA in HLA-B27-positive Japanese individuals.