The genetics of systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a disease characterised by diverse clinical manifestations and the presence of multiple autoantibodies. There are multiple aetiological factors involved in its pathogenesis. Genetic factors do play an important role and the major histocompatibility complex has been studied extensively and many human leukocyte antigen (HLA) associations have been reported. Twin and familial lupus studies confirm the importance of genetic factors in the development of SLE. Reported HLA associations range from that of HLA-DR3 in Caucasians to HLA-DR2 in Chinese, Japanese and American Blacks. These associations however may only represent linkage disequilibrium and not the actual susceptibility genes. Other non-major histocompatibility complex genes have also been reported to play important roles in the pathogenesis of lupus. The advent of molecular biological techniques has advanced the understanding of susceptibility genes in many diseases. The use of microsatellite genome scanning to study multiplex lupus families has yielded a wealth of information on clusters of susceptibility genes. The identification of these genes will be an important advance in the understanding of this complex disease.