HOMOZYGOSITY FOR THE HLA-DR SHARED EPITOPE CONTRIBUTES THE HIGHEST RISK FOR RHEUMATOID-ARTHRITIS CONCORDANCE IN IDENTICAL-TWINS

Objective. To assess the contribution of HLA-DRB1 alleles in determini ng rheumatoid arthritis (RA) concordance in monozygotic twins. Methods . Ninety-one monozygotic twins pairs in which at least 1 twin was affe cted were typed for HLA-DRB1 using both serologic methods and polymera se chain reaction amplification with sequence-specific oligonucleotide hybridization. The role of DR4 and of the shared epitope in disease c oncordance was investigated. Relative risks (RR) with 95% confidence i ntervals were determined. Results. Increased concordance for RA was ob served in both DR4 positive and shared epitope positive pairs (RR 3.4 and 3.7, respectively). A 5-fold risk for RA concordance was seen in t wins who were ''homozygous'' for the shared epitope, compared with tho se negative for the shared epitope. Conclusion. In the absence of the shared epitope, RA concordance in monozygotic twins is rare. In contra st, ''homozygosity'' for the shared epitope is the most important fact or in determining RA concordance.