V Moos1, J Menard, J Sieper, M Sparmann, B Müller. 1. Deutsches Rheuma Forschungs Zentrum Berlin, Department of Medicine, Division of Nephrology and Rheumatology, Klinikum Benjamin Franklin, Free University, Berlin, Germany.
Abstract
OBJECTIVE: We have previously shown that the inflammatory cytokines tumour necrosis factor alpha (TNF-alpha) and interleukin (IL) 6 or IL-1beta are up-regulated in chondrocytes of patients with osteoarthritis (OA). However, the inflammatory responses associated with OA are of low grade and restricted. To investigate the involvement of the immune system in the pathogenesis of OA, we analysed patients for their HLA-DRB1 haplotypes. METHODS: Combining single-stranded oligo or sequence-specific primer typing procedures, 139 randomly selected controls and 106 OA patients were typed for their HLA-DRB1 alleles. RESULTS: The OA cohort showed statistically significant differences in the frequencies of the DR2 and DR5 alleles compared with the controls. While the frequency of the DR2 allele was elevated among the OA patients, the DR5 allele was negatively associated with the disease. The P values for differences from the controls were 0.0431 for DR2 and 0.0386 for DR5 and the odds ratios for the two alleles were 1.58 and 0.54 respectively. CONCLUSION: The association of DR2 and DR5 with OA hints at linkage disequilibrium between HLA-DRB1 genes and genes involved in the pathogenesis of OA. Alternatively, DR2 has a direct role in restricting immunological responses to the low-grade inflammation characteristic of OA.
OBJECTIVE: We have previously shown that the inflammatory cytokines tumour necrosis factor alpha (TNF-alpha) and interleukin (IL) 6 or IL-1beta are up-regulated in chondrocytes of patients with osteoarthritis (OA). However, the inflammatory responses associated with OA are of low grade and restricted. To investigate the involvement of the immune system in the pathogenesis of OA, we analysed patients for their HLA-DRB1 haplotypes. METHODS: Combining single-stranded oligo or sequence-specific primer typing procedures, 139 randomly selected controls and 106 OA patients were typed for their HLA-DRB1 alleles. RESULTS: The OA cohort showed statistically significant differences in the frequencies of the DR2 and DR5 alleles compared with the controls. While the frequency of the DR2 allele was elevated among the OA patients, the DR5 allele was negatively associated with the disease. The P values for differences from the controls were 0.0431 for DR2 and 0.0386 for DR5 and the odds ratios for the two alleles were 1.58 and 0.54 respectively. CONCLUSION: The association of DR2 and DR5 with OA hints at linkage disequilibrium between HLA-DRB1 genes and genes involved in the pathogenesis of OA. Alternatively, DR2 has a direct role in restricting immunological responses to the low-grade inflammation characteristic of OA.