V Pittoni1, D Isenberg. 1. Centre for Rheumatology, Department of Medicine, University College of London, UK.
Abstract
OBJECTIVE: To analyze the potential links between antiphospholipid antibodies (aPL) and apoptosis in the pathogenesis of the antiphospholipid antibody syndrome (APS). METHODS: A review was undertaken of the most relevant scientific literature on apoptosis and autoimmune phenomena. Experimental and human pathology were reviewed to substantiate the hypothesis that apoptosis is involved in the generation of aPL. RESULTS: Several considerations suggest that exposure of phospholipids (PL) during apoptosis may be a driving antigenic stimulus to the production of aPL. Furthermore, the molecular PL-protein complexes formed during apoptosis are targeted by "pathogenic" aPL. The binding and the clearance of apoptotic cells by these autoantibodies likely further enhances the aPL immune response. Experimental models and human pathology suggest that a restricted genetic background is key to the development of this immune response. CONCLUSIONS: Abnormalities of apoptosis observed in the course of autoimmune conditions likely provide an antigenic stimulus to the production of aPL.
OBJECTIVE: To analyze the potential links between antiphospholipid antibodies (aPL) and apoptosis in the pathogenesis of the antiphospholipid antibody syndrome (APS). METHODS: A review was undertaken of the most relevant scientific literature on apoptosis and autoimmune phenomena. Experimental and human pathology were reviewed to substantiate the hypothesis that apoptosis is involved in the generation of aPL. RESULTS: Several considerations suggest that exposure of phospholipids (PL) during apoptosis may be a driving antigenic stimulus to the production of aPL. Furthermore, the molecular PL-protein complexes formed during apoptosis are targeted by "pathogenic" aPL. The binding and the clearance of apoptotic cells by these autoantibodies likely further enhances the aPL immune response. Experimental models and human pathology suggest that a restricted genetic background is key to the development of this immune response. CONCLUSIONS: Abnormalities of apoptosis observed in the course of autoimmune conditions likely provide an antigenic stimulus to the production of aPL.