The genetics of lupus.

Abstract

The complex multifactorial inheritance pattern of systemic lupus erythematosus in various murine models has been dissected via both classic genetic analysis and the use of modern technologies in genomic manipulation. Current information suggests that lupus may be mediated by a multitude of genetic abnormalities that impact on specific checkpoints in a three-step pathogenic pathway. These steps are as follows: loss of immunologic tolerance to nuclear antigens; the transition to pathogenic autoimmunity; and end-organ targeting. The identities of the genes that are responsible for transition between the specific steps of the pathway are still unknown and will require further study. However, several recent findings have provided insights into specific elements in each stage of lupus. These findings suggest that mouse models of lupus may provide valuable insights into the genetic basis of human systemic lupus erythematosus.