ABSTRACT
The etiology of systemic lupus erythematosus is still unknown, but genetic predilection appears to be a dominant factor. Therefore, elucidation of the genes and their contibutions to the development of lupus should reveal many of the fundamental events underlying the initiation and maintenance of systemic autoimmunity. Identification of the genetic alterations that enhance susceptibility will directly define the causative mechanisms that lead to immune system-mediated self-destruction. Identification of the normal genes involved in the immunological and inflammatory processes that promote end-organ damage will reveal the components crucial for disease manifestations, which can provide targets for therapeutic intervention. Progress in delineating specific genes and pathways participating in immune system activation and homeostasis, along with gene manipulation approaches, have identified many new potential avenues for loss of tolerance and development of systemic autoimmunity. Never has the genetic basis for systemic autoimmunity been documented more clearly and yet, ironically, this progress has also revealed the enormous gaps in our understanding of this complex process. This chapter will focus primarily on new findings since the last edition and will summarize our current view of this rapidly evolving field.
