THE ASSOCIATION OF THE HLA-DRB1 GENE WITH RHEUMATOID-ARTHRITIS

The association between rheumatoid arthritis (RA) and the HLA-DR4 is k nown since 1978. However, the significance of the HLA-DR4 for the path ogenesis of RA has not been uniformly accepted. Further studies reveal ed that also other HLA-DR alleles were associated with RA. With the ap plication of molecular biology techniques, it could be demonstrated th at the serologically typed HLA-DR4 allele consists of different allele s. Only some of them predispose for RA. These predisposing alleles sha re a conserved aminoacid sequence of the 3(rd) hypervariable region of the HLA-DRB1 gene at positions 70-74 and 86. This RA-associated seque nce is called ''Shaped Epitope'' (SE). This SE is conserved not only b etween associated HLA-DR4 alleles, but between all HLA-DR-alleles whic h predispose for RA. Patients homozygous for the SE appear to have a m ore severe disease course than heterozygous patients. These data are b ased mainly on the results of cross-sectional studies. The value of HL A-DR alleles as prognostic markers for RA has to be investigated furth er in prospective studies.