Shared epitopes and rheumatoid arthritis: Disease associations in Greece and meta-analysis of Mediterranean European populations

Objectives: To assess the strength of the associations between HLA shared epitopes (SE) and rheumatoid arthritis (RA) susceptibility, articular disease severity, and extra-articular features in Mediterranean European populations. Methods: One hundred and seventy-four Greek RA patients and 103 controls were evaluated. Data were then included in a meta-analysis of 9 studies of Mediterranean European populations (959 RA patients and 1,405 controls). Results: In our study population, SE alleles were significantly more common in RA patients than in controls (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.4-4.3). Larsen radiologic score was predicted by SE and disease duration. SE did not increase the risk of any extra-articular manifestation. The meta-analysis showed a pooled OR of 3.7 (95% Cl, 2.6-5.2) for susceptibility to RA conferred by SE (OR, 3.4 v 3.9 in Greek v non-Greek populations). Conclusions: SE determine articular destruction without increasing the risk of extra-articular manifestations. The immunogenetic associations of RA susceptibility are consistent, but their strength may depend on the SE prevalence in different ethnic groups.