Lupus: Key pathogenic mechanisms and contributing factors

The past 30 years of research on murine and human systemic lupus erythematosus has served to identify an array of immunological aberrations-some shared, some unique, some primary, others secondary-that may underlie this disease. In integrating these findings, it appears that at least four distinct pathogenic events characterize lupus: (1) Anti-DNA Abs and immune complexes induce renal damage; (2) B-cells produce pathogenic anti-DNA antibodies; (3) Th cells drive lupus B-cells; and (4) Increased concentrations and abnormal presentation of nucleosomes. The purpose of this review is to examine the roles of these four events in the pathogenesis of lupus and to identify the different factors that can precipitate these pathogenic events.