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 determining rheumatoid arthritis (RA) concordance in monozygotic twins. Methods. Ninety-one monozygotic twins pairs in which at least 1 twin was affected were typed for HLA-DRB1 using both serologic methods and polymerase chain reaction amplification with sequence-specific oligonucleotide hybridization. The role of DR4 and of the shared epitope in disease concordance was investigated. Relative risks (RR) with 95% confidence intervals were determined. Results. Increased concordance for RA was observed 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 twins who were ''homozygous'' for the shared epitope, compared with those negative for the shared epitope. Conclusion. In the absence of the shared epitope, RA concordance in monozygotic twins is rare. In contrast, ''homozygosity'' for the shared epitope is the most important factor in determining RA concordance.