The relationship between genetics and environment in the pathogenesis of rheumatic diseases

Abstract

Major developments have taken place to further our understanding of the relationship between genetics and the environment in the pathogenesis of rheumatic disorders. The association between HLA markers and human disease is becoming clearer. For instance, HLA-DRW4 frequently occurs in patients with rheumatoid disease, and penicillamine and gold toxicity are seen most often in patients with HLA-DRW2 or DRW3. Antisera to B alloantigens help define the genetic differences between systemic lupus erythematosus and rheumatoid arthritis. As yet, the most dramatic link is that between HLA-B27 and primary ankylosing spondylitis. This same antigen is related, to varying degrees, with other members of the seronegative spondylarthritides and there is strong evidence that this association is related to HLA-B27, itself, rather than an associated disease gene. Nevertheless, some data refute a single gene theory. We are just beginning to learn more about interactions between different genes on the sixth chromosome and genes on other chromosomes.The sex ratio of the spondylarthritides is now better defined. Sacroiliitis may have a comparable sex distribution although females have more peripheral joint disease and males have greater spinal involvement. Unfortunately, the explanation for these differences remains elusive.The specific infective agents related to the development of rheumatic disorders are becoming clarified. Chlamydia, Salmonella, Yersinia and Shigella flexneri types 1b and 2a are arthritogenic, while Shigella sonnei appears not to cause disease. Although the Reiter syndrome is now considered a chronic disease, the reason for remissions and relapses remains unclear.