The role of HLA-DR-DR and HLA-DR-DP interactions in genetic susceptibility to rheumatoid arthritis

Abstract

In order ro 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 DRβ1 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 β1 chain (82% vs 56% in controls, p < 0.008), with a twofold increased risk of RA. Our results suggest a role of HLA-DR-DR and -DR-DP interactions in the genetic susceptibility to RA.