Elimination of Nucleoproteins in Systemic Lupus Erythematosus and Antinuclear Autoantibodies Production

Abstract

The distinctive feature of systemic lupus erythematosus (SLE) is an immune reaction directed to diverse spectrum of autoantigens, which tends to change along with the disease spreading. The most common targets of the autoantibodies are protein and nucleoprotein components of cell nuclei: dsDNA, histones, nucleosomes, Sm antigen, and Ro and La antigens. Considering that the exact causes of this tolerance loss are unknown, a certain number of hypotheses are now discussed. One of the most promising is "waste disposal" concept, which makes a link between broken elimination of cellular debris, mononuclear phagocyte system dysfunction, and initiation of autoimmunity by the antigen presenting cells in SLE. This chapter concerns the ways nuclear antigens release from cells, necrosis, and apoptosis, as well as the key molecular mechanisms of transport and elimination of these antigens, its disturbances in SLE, and connection with innate immunity by mononuclear cells. Special atention is paid to nucleosomes and DNA degradation process, its principal factors (DNase I, C1q, SAP), blood DNA transportation by immune complexes, and immune stimulating action of DNA in SLE. Current pros and cons for the waste disposal concept and existing research trends in this ield are discussed.