This is important since some HLA-DRB1*04 variants are associated with RA (i.e. HLA-DRB1*04:01, 04:04, and 04:05), while others have been found to be protective against RA development and severity (i.e. HLA-DRB1*04:02). This evidence concerns the gene HLA-DRB1 and rheumatoid arthritis.