We propose to classify HLA-DRB1 alleles into 3 groups: shared epitope positive (SE), shared epitope negative with a positively charged HLA-DR P4 pocket (XP4p) and shared epitope negative with a negative or neutral HLA-DR XP4 pocket (XP4n). Using this classification to analyse 3 different French populations, we find that:
-SE/SE or SE/XP4p genotypes are associated with a high risk to develop RA.
-XP4p/XP4p or SE/XP4n genotypes are neutral
-XP4p/XP4p or XP4n/XP4n genotypes are protective with respect to the development of RA.