THE ROLE OF HLA-DR-DR AND HLA-DR-DP INTERACTIONS IN GENETIC SUSCEPTIBILITY TO RHEUMATOID-ARTHRITIS

In order to analyze the relationships between the DR and DP loci in th e genetic susceptibility ro RA, HLA-DRB1 and -DPB1 polymorphism was st udied in 155 RA patients compared to 250 controls, using a reverse dot -blot analysis. Our data were consistent with the involvement of the a mino acid in position 71 of the third hypervariable region of the DR b eta 1 chain in susceptibility to the disease. The higher risk for RA w as observed in patients who carried the association of a lysine (K), c haracterizing the DRB10401 susceptibility allele, with an arginine (R ), observed in ail the other DRB1 susceptibility alleles (21.9% vs 0. 6%, p(c) < 10(-6), OR = 42). In the absence of arginine, the presence of lysine was still associated with the disease (33% vs 19%, p(c) < 0. 03, OR = 2). In contrast, in the absence of lysine, the frequency of a rginine in position 71 was similar in patients and controls (30% vs 26 %, p = NS). On another hand, the analysis of the HLA-DPB1 locus showed that the DPB10401 allele frequency was significantly increased in th e RA patient group (n = 47) who expressed only arginine at the positio n 71 of the beta 1 chain (82% vs 56% in controls, p < 0.008), with a t wofold increased risk of RA. Our results suggest a role of HLA-DR-DR a nd -DR-DP interactions in the genetic susceptibility to RA.