HLA class II encodes for DR, DQ, and DP loci (classical regions) and DM and DO loci (non-classical regions) where allelic combinations exist in the classical DR regions within the third hypervariable region (HVR3) of the HLA-DRB1 chain termed as shared epitopes (SEs), showing an increased risk for developing RA (24, 25). This evidence concerns the gene HLA-DRB1 and rheumatoid arthritis.