title: Activation of complement mediates antiphospholipid antibody-induced pregnancy loss.
abstract: Although it is clear that the specific antigenic reactivity of antiphospholipid (aPL) antibodies is critical to their effect, the pathogenic mechanisms that result in injury in vivo are incompletely understood. We hyphothesized that aPL antibodies targeted to the placenta activate complement locally, generating split products that mediate placental injury and lead to foetal loss and growth retardation. To test this hypothesis, we used a murine model of APS in which pregnant mice are injected with human IgG containing aPL antibodies. Mice treated with inhibitors of complement activation and mice deficient in complement components were protected from aPL antibody-induced foetal damage. Although the cause of tissue injury in this disease is probably multifactoral, we have shown that complement activation is an absolute requirement for foetal loss and growth restriction and, therefore, thatthis pathway acts upstream of other important effector mechanisms. Identification of complement activation as a mechanism that is necessary for aPL-induced tissue damage and definition ofthe complement components necessary to trigger such injury is likely to lead to a better understanding of the pathogenesis of vascular and tissue injury in SLE and to new and improved treatments.
authors.affiliation: Department of Medicine, Hospital for Special Surgery-Weill Medical College, Cornell University, New York, NY 10021, USA. salmonj@hss.edu
authors.forename: J E
authors.initials: JE
authors.lastname: Salmon
authors.forename: G
authors.initials: G
authors.lastname: Girardi
authors.forename: V M
authors.initials: VM
authors.lastname: Holers
mesh_terms: D000022:Abortion, Spontaneous / Q000209:etiology / Q000276:immunology*; D000818:Animals; D017152:Antibodies, Antiphospholipid / Q000276:immunology*; D003167:Complement Activation / Q000276:immunology*; D003176:Complement C3 / Q000276:immunology; D005260:Female; D005317:Fetal Growth Retardation / Q000209:etiology / Q000276:immunology; D005333:Fetus / Q000276:immunology; D006801:Humans; D010920:Placenta / Q000276:immunology; D011247:Pregnancy
chemical_list: D017152:Antibodies, Antiphospholipid; D003176:Complement C3