Apoptosis in the pathogenesis of systemic lupus erythematosus.

Abstract

Systemic lupus erythematosus (SLE) is a prototype inflammatory autoimmune disease resulting from autoimmune responses against nuclear autoantigens. During apoptosis many lupus autoantigens congregate inside the cells and are susceptible to modifications. Modified nuclear constituents are considered foreign and dangerous. Therefore, apoptotic cells have to has to be efficiently removed to avoid the accumulation of apoptotic debris and the subsequently development of autoimmune responses. Hence, apoptosis and clearance of apoptotic cells/material are considered key processes in the aetiology of SLE. Clearance deficiencies may account for the development of autoimmunity by inducing a loss of tolerance in lymphoid tissues. Furthermore, phagocytosis of apoptotic cells may lead to a pro-inflammatory response in the presence of autoantibodies. This may sustain inflammatory conditions and the pathology found in overt lupus.