The Immunopathogenesis and Immunopathology of Systemic Lupus Erythematosus
Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by the production of antinuclear antibodies (ANAs). These antibodies can bind protein and nucleic acid components of the cell nucleus to form immune complexes to drive pathogenesis. These complexes can deposit in the kidney to incite nephritis or stimulate plasmacytoid dendritic cells (pDCs) to produce cytokines, most prominently type 1 interferon. The activity of the complexes reflects the intrinsic immunostimulatory properties of nucleic acids, both DNA and RNA, which can activate the innate immune system by interaction with toll-like receptors (TLRs) as well as non-TLR sensors. The operation of this system requires the presence of extracellular nucleic acids which can be derived from apoptotic and necrotic cells. With impaired clearance of dead and dying cells, levels of extracellular nucleic acids can rise and intensify immune disturbances key to autoimmunity.
KeywordsSystemic Lupus Erythematosus Immune Complex Autoantibody Production Congenital Heart Block Human Lupus