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 the genetic susceptibility to RA, HLA-DRB1 and -DPB1 polymorphism was studied in 155 RA patients compared to 150 controls, using a reverse dot-blot analysis. Our data were consistent with the involvement of the amino acid in position 71 of the third hypervariable region of the DR beta 1 chain in susceptibility to the disease. The higher risk for RA was observed in patients who carried the association of a lysine (K), characterizing the DRB1* 0401 susceptibility allele, with an arginine (R), observed in all 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 arginine 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 DPB1 *0401 allele frequency was significantly increased in the RA patient group (n = 47) who expressed only arginine at the position 71 of the beta 1 chain (82% vs 56% in controls, p < 0.008), with role of HLA-DR--DR and -DR-DP interactions in the genetic susceptibility to RA.