ABSTRACT
Systemic lupus erythematosus (SLE) is a very heterogeneous chronic infl ammatory autoimmune disease with a plethora of symptoms and clinical signs. Th e exact development of SLE is still unclear; however, it is known that its etiopathogenesis is of multifactorial nature. Th e main characteristic of this disease is the production of autoantibodies (AAb) targeting double stranded DNA (dsDNA) and other nuclear autoantigens. Th e latter target antigens that are modifi ed and or translocated when apoptotic cells enter the stage of secondary necrosis, oft en due to clearance defi ciency. Under healthy conditions, dead and dying cells are rapidly removed by phagocytes releasing anti-infl ammatory cytokines without eliciting immune responses. In SLE, apoptotic cells are oft en not cleared on time and the leaked autoantigens are presented to B cells by follicular dendritic cells (FDC) in secondary lymphoid tissues. Th is process challenges the peripheral selftolerance. Autoreactive B cell activation contributes to production of antinuclear AAb and formation of immune complexes (IC) with the non-properly cleared nuclear autoantigens that may be generated or deposited in various tissues. Under certain circumstances IC may also be ingested by phagocytes, which subsequently produce pro-infl ammatory cytokines. Th ese processes result in chronic organ and
tissue damage and in the development as well as the maintenance of the systemic autoimmune disease (Fig. 1).
