HLA associations are with severe rheumatoid arthritis

Rheumatoid arthritis (RA) has been studied in 17 multicase families from the North East of England. The families comprised 281 individuals, 51 of whom had classical or definite RA, 18 had probable RA, and six were classified as previous RA. The association of classical and definite RA with HLA-DR4 was confirmed, and homozygosity for DR4 was more strongly associated than heterozygosity. There was a trend towards negative association with HLA-DR2 and DR7. Homozygosity for DR4 and possession of the haplotype most frequently inherited with RA in a particular family showed association with more severe disease. HLA-DR2 and DR7 tended to associate with less severe disease. It is therefore likely that HLA association is with the severity of disease rather than disease susceptibility.