Rheumatoid arthritis: Relationship with HLA-D

Understanding of the genetic component of rheumatoid arthritis has been greatly enhanced by the discovery of the association of risk for development of this disease with certain histocompatibility antigens. The HLA-D region, at the centromeric end of the HLA gene complex, on the short arm of chromosome number 6, is concerned with important functions in the regulation of the Immune response. The products of the HLA-D region (DR, SB, MT, and the like) function as "restriction elements" for antigen presentation, mediators of immune response and immune suppressor genes, stimulators of graft rejection, and of other allogenic effects. Rheumatoid arthritis is associated with Dw4 and DR4 in Caucasians. The association with DR4 has been observed also in Blacks and Orientals. HLA-DR4 is associated with more severe, rheumatoid factor-positive disease. Clinical and genetic heterogeneity has been revealed by studies of patients with juvenile arthritis. Conditions often associated with rheumatoid arthritis and also thought to have an immunologic basis, such as Sjögren's syndrome, Felty's syndrome, and rheumatoid vasculitis, and reactions to medications, such as gold and penicillamine, reveal an interesting spectrum of immunogenetic relationships. Thus, HLA studies have shed light on the classification of patients with rheumatoid diseases. In view of the role of HLA-D in the immune response, these studies are expected to further our understanding of the mechanism underlying predisposition for development of rheumatoid arthritis and related conditions.