[New aspects of the pathogenesis of systemic lupus erythematosus].
To date, the pathogenesis of systemic lupus erythematosus (SLE) is only partially understood. A characteristic feature of this disease is the occurrence of antibodies against nuclear antigens. Further, SLE is characterized by a type-I interferon gene signature. A dysregulation of apoptosis and phagocytosis of apoptotic cells is discussed as a central pathogenetic mechanism in the development of SLE. Several publications in recent years have described an accumulation of autoantigens within apoptotic cells, as well as an exposition of these antigens on the surface of apoptotic cells. During late stages of apoptosis, autoantigens are posttranslationally modified, leading to the formation of neoantigens. Subcellular fragments such as apoptotic microparticles also seem to be involved in the pathogenesis of SLE. It has been shown that microparticles contain relevant antigens and stimulate B- and T-lymphocytes. Moreover, apoptotic microparticles have the ability to stimulate plasmacytoid dendritic cells, causing a secretion of interferon alpha. These observations provide a link between dysregulation of apoptosis and phagocytosis and the type-I interferon signature observed in SLE patients.
Schiller
M
M
Sektion Rheumatologie, Medizinische Klinik V, Universität Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Deutschland. martin.schiller@med.uni-heidelberg.de
Lorenz
H-M
HM
Blank
N
N
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001324:Autoantigens / Q000276:immunology*; D002462:Cell Membrane / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D004195:Disease Models, Animal; D006801:Humans; D016898:Interferon-alpha / Q000097:blood; D007962:Leukocytes / Q000276:immunology*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D010316:Particle Size; D010586:Phagocytes / Q000276:immunology; D013347:Subcellular Fractions / Q000276:immunology
D001324:Autoantigens; D016898:Interferon-alpha