The term “shared epitope” most commonly refers to a five amino acid sequence motif in residues 70-74 of the DR chain coded by several HLA-DRB1 alleles that are overpresented among patients with remathoid arthritis. The shared epitope motif consists of three homologous amino acid sequence variants.
- QKRAA, the shared epitope variant that is the most common motif among Caucasian is coded primarily by the HLA-DRB1*0401 allele
- The second most common motif, QRRAA, is coded by several alleles, among them HLA DRB1*0404, DLA-DRB1*0101 and HLA-DRB1*0405
- The third motif, RRRAA, coded by allele HLA-DRB1*1001, is the rarest
In addition to increasing remathoid arthritis risk, shared epitope coding HLA-DRB1 alleles have been shown to associate with more severe disease and to exhibit allele-dose effect, that is patients with two shared epitope coding alleles tend to experience more severe disease than patients with one allele, who, in turn, have more severe remathoid arthritis than shared epitope-negative.