Systemic lupus erythematosus and apoptosis: a question of balance.
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by the presence of autoantibodies directed against a range of intracellular nucleoprotein targets. SLE patients are believed to develop an autoimmune response triggered by surface-exposed intracellular macromolecules translocated to the cell surface during apoptosis. Apoptosis-or programmed cell death-is a genetically controlled process initiated by two principal pathways. The extrinsic pathway is activated by the ligation of death receptors, and the intrinsic pathway emerges from mitochondria. As shown in fas-deficient mice and humans, the inability of the immune system to eliminate self-reactive lymphocytes by apoptosis can cause persistence of autoreactive cells and autoimmunity. However, as shown in complement deficiencies, increased apoptotic material and altered clearance of apoptotic cells is found in patients with SLE. These results suggest that what is found in rare individuals with genetic deficiencies that develop SLE or SLE-like disease may be found in the larger population of SLE patients as a common end point pattern of unbalanced process of both apoptosis and clearance of apoptotic material.
Mevorach
Dror
D
The Lab for Cellular and Molecular Immunology, Rheumatology Unit, Hebrew University, Jerusalem 91220, Israel. mevorachd@hadassah.org.il
D017209:Apoptosis / Q000276:immunology / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D015551:Autoimmunity / Q000276:immunology; D000072224:Bcl-2-Like Protein 11; D002352:Carrier Proteins / Q000502:physiology; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000503:physiopathology*; D008565:Membrane Proteins; D008928:Mitochondria / Q000502:physiology; D011518:Proto-Oncogene Proteins; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; D002352:Carrier Proteins; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D014409:Tumor Necrosis Factor-alpha