title: Complement activation: a novel pathogenic mechanism in the antiphospholipid syndrome.
abstract: Antiphospholipid antibodies (aPLs) have been shown to induce thrombosis, activate endothelial cells, and induce fetal loss. The pathogenesis of aPL-induced thrombosis is incompletely understood, but it is thought to involve platelet and endothelial cell activation as well as pro-coagulant effects of aPL antibody directly on clotting pathway components. Recent studies have shown that uncontrolled complement activation leads to fetal death in aPL-antibody treated mice. We hypothesized that aPL antibodies activate complement, generating split products that induce thrombosis. To test this hypothesis, we used an in vivo model of thrombosis in which aPL antibodies induce a significant increase in thrombus size and a mouse model of endothelial cell activation in which aPLs induce significant adhesion of leukocytes (WBCs) to endothelial cells. We found that mice deficient in complement components C3 and C5 were resistant to enhanced thrombosis and endothelial cell activation induced by aPL antibodies. Furthermore, inhibition of C5 activation using anti-C5 mAb prevented thrombophilia induced by aPL antibodies. Our data show that complement activation mediates two important effectors of aPL antibodies: induction of thrombosis and endothelial activation.
authors.affiliation: Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, 720 Westview Drive SW, Atlanta, GA 30310-1495, USA. spierangeli@msm.edu
authors.forename: Silvia S
authors.initials: SS
authors.lastname: Pierangeli
authors.forename: Mariano
authors.initials: M
authors.lastname: Vega-Ostertag
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Liu
authors.forename: Guillermina
authors.initials: G
authors.lastname: Girardi
mesh_terms: D000818:Animals; D017152:Antibodies, Antiphospholipid / Q000097:blood; D016736:Antiphospholipid Syndrome / Q000209:etiology* / Q000276:immunology / Q000628:therapy; D003167:Complement Activation; D003176:Complement C3 / Q000502:physiology; D003182:Complement C5 / Q000502:physiology; D006801:Humans; D051379:Mice; D013927:Thrombosis / Q000517:prevention & control
chemical_list: D017152:Antibodies, Antiphospholipid; D003176:Complement C3; D003182:Complement C5