Clearance deficiency--a potential link between infections and autoimmunity.
Cell death plays a pivotal role in development and homeostasis of multicellular organisms. Apoptosis represents the physiological and anti-inflammatory form of cell death. Advanced apoptosis and necrosis are rather pro-inflammatory. Several "find-me"- and "eat-me"-signals support the "swift and silent" removal of dying cells. If the highly controlled process of dying cell removal fails, they may progress to secondary necrosis and provoke autoimmunity. There are several reports describing clearance deficiency as a possible mechanism in the etiopathogenesis of SLE. Under certain conditions, increased phagocytosis of nuclear material may be found in a subgroup of patients with SLE. Complement proteins and autoantibodies may modify engulfment of apoptotic remnants and shift the clearance process towards inflammation. Taken together, clearance deficiency leads to the accumulation of apoptotic remnants and breaking of tolerance to self. Besides, enhanced uptake of nuclear immune complexes may maintain chronic autoimmunity in patients with SLE.
Schulze
C
C
Institute for Clinical Immunology and Rheumatology, Department of Internal Medicine 3, Friedrich-Alexander University of Erlangen-Nuremberg, 91054 Erlangen, Germany.
Munoz
L E
LE
Franz
S
S
Sarter
K
K
Chaurio
R A
RA
Gaipl
U S
US
Herrmann
M
M
D000818:Animals; D017951:Antigen Presentation; D034961:Antigens, Nuclear / Q000378:metabolism; D017209:Apoptosis / Q000276:immunology*; D001323:Autoantibodies / Q000096:biosynthesis / Q000378:metabolism*; D015551:Autoimmunity; D003165:Complement System Proteins / Q000378:metabolism*; D003602:Cytotoxicity, Immunologic; D006706:Homeostasis; D006801:Humans; D007110:Immunity, Active; D007239:Infections / Q000150:complications / Q000276:immunology*; D007249:Inflammation; D008180:Lupus Erythematosus, Systemic / Q000209:etiology; D009336:Necrosis; D010587:Phagocytosis / Q000276:immunology*
D034961:Antigens, Nuclear; D001323:Autoantibodies; D003165:Complement System Proteins