HLA-DQβ 3.1 allele is a determinant of susceptibility to DR4-associated rheumatoid arthritis (original) (raw)

Rheumatoid arthritis is associated with HLA-DR4 in several ethnic groups. Since DR4 haplotypes encode a diverse array of class II molecules, it is of interest to characterize the nature of the primary association. We have examined molecular polymorphisms of HLA class II gene products expressed by normals and rheumatoid arthritis patients using monoclonal antibodies and two-dimensional electrophoresis. Most homozygous DR4 rheumatoid arthritis patients express DR~I molecules associated with Dw4 or DwI4 mixed lymphocyte culture determinants. In Caucasoids, two DR4-1inked DQw3-associated [3-chain alleles are defined by two-dimensional electrophoresis. These variants, designated DQ[3 3.1 and 3.2, are associated with the serologic determinants DQw7 and DQw8, respectively. A panel of 40 DR4-posith,e normals was also examined for nucleotide sequence polymorphisms associated with DQB3.1 and 3.2 genes using the polymerase chain reaction and specific oligonucleotide probes. At the DQ[3 level the rheumatoid arthritis panel was distinguished by enrichment for the DQ[3 3.1 allele with 100% of patients positive for DQw7. Results presented here suggest that specific DQfl alleles may modify the effect of HLA-DR4[31 alleles in conferring susceptibility to rheumatoid arthritis in a phenotype-specific fashion.