Evidence for linkage of HLA loci in juvenile idiopathic oligoarthritis: independent effects of HLA-A and HLA-DRB1

OBJECTIVE: Although multiple associations between HLA loci and juvenile oligoarthritis have previously been documented, evidence for linkage of HLA loci in oligoarthritis in UK Caucasians with juvenile idiopathic arthritis (JIA) has not been described. The aim of this study was to investigate linkage of HLA-A, B, and DRB1 in UK Caucasian JIA patients with oligoarthritis. METHODS: One hundred forty-two families comprising affected offspring and their parents (45 with one parent available and 97 with both parents available) were typed for HLA-A, B, and DRB1 by polymerase chain reaction-sequence-specific oligonucleotide probe. Single-point and multipoint analyses were performed using various modifications of the extended transmission disequilibrium test. Linkage disequilibrium (LD) analysis was performed using the EH-Plus system. RESULTS: Linkage to HLA-A and HLA-DRB1 was seen in oligoarthritis and in the International League of Associations for Rheumatology-defined subgroups of persistent oligoarthritis and extended oligoarthritis. Linkage to HLA-A, B, and DRB1 was also observed in female patients with oligoarthritis. Linkage of the HLA loci seemed to be attributable to maternal preferential transmission of alleles. Furthermore, LD patterns between the HLA-A, B, and DRB1 loci were investigated. HLA-A and HLA-DRB1 were confirmed as independent susceptibility loci for oligoarthritis. CONCLUSION: This is the first study to establish linkage of HLA-A and HLA-DRB1 in oligoarthritis and to show that the 2 loci contribute independently to disease. Further studies are being performed to determine whether it is these loci or other genes in LD with them that are responsible for susceptibility to oligoarthritis in UK Caucasian patients with JIA.