Pathogenesis of Systemic Lupus Erythematosus

Pathogenesis of Systemic Lupus Erythematosus remains unsolved. A variety of new experimental data suggests that a dysfunction of apoptosis might be involved in the initiation of autoimmunity finally leading to SLE. This includes signalling alterations in activated lymphocytes (leading to premature apoptosis), defects in the clearance of apoptotic material and genetic defects in the complement system. These mechanisms lead to an increased onflow of apoptotic or secondary necrotic material which will be recognized by immunocompetent cells. Especially, concomitant infections in the context of genetic variations like Fc gamma- or IL-8 polymorphisms, will further induce T- and B-cell activation, synthesis of ANA or anti-ds-DNA antibodies, and finally precipitate the onset of the disease. Estrogens might directly modulate the immune response and therefore favour a shift to a lupus-prone state.