Complement C3 Activation Is Required for Antiphospholipid Antibody-induced Fetal Loss
By Michael Holers, G. Girardi, L. Mo, J. Guthridge, Héctor Molina, S. Pierangeli, R. Espinola, Xiaowei Liu, D. Mao, Christopher G. Vialpando and 1 more. Journal of Experimental Medicine, 2002
628 citations recorded by the source corpus.
The antiphospholipid syndrome (APS) is characterized by recurrent fetal loss, vascular thrombosis, and thrombocytopenia occurring in the presence of antiphospholipid (aPL) antibodies. The pathogenesis of fetal loss and tissue injury in APS is incompletely understood, but is thought to involve platelet and endothelial cell activation as well as procoagulant effects of aPL antibodies acting directly on clotting pathway components. Recent studies have shown that uncontrolled complement activation in the placenta leads to fetal death in utero. We hypothesized that aPL antibodies activate complement in the placenta, generating split products that mediate placental injury and lead to fetal 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. We found that inhibition of the complement cascade in vivo, using the C3 convertase inhibitor complement receptor 1–related gene/protein y (Crry)-Ig, blocks fetal loss and growth retardation. Furthermore, mice deficient in complement C3 were resistant to fetal injury induced by aPL antibodies. While antigenic epitopes recognized by aPL antibodies are important in the pathogenesis of APS, our data show that in vivo complement activation is required for aPL antibody-induced fetal loss and growth retardation.
Subfields: Hematology, Immunology, Rheumatology
View Paper: https://www.semanticscholar.org/paper/19967e7c0da49eddbc57c14677bb55f3453f381d
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Citations in the corpus
- Pathogenesis of antiphospholipid syndrome: understanding the antibodies (2011, background): “Immunohistochemical and histological examination of decidua showed deposition of human IgG and mouse complement, neutrophil infiltration and local TNF secretion, in association with a transient but significant increase in blood TNF levels”
- Complement and coagulation: strangers or partners in crime? (2007, background): “Furthermore, mice deficient in C3 or treated with inhibitors of complement activation are protected from fetal loss [54, 55 ].”
- Complement C5a receptors and neutrophils mediate fetal injury in the antiphospholipid syndrome. (2003, methodology): “The complement pathway presents a second Fc-dependent means of effecting Abmediated injury, and our initial studies showed that blocking C3 prevents fetal loss in murine APS (17).”
- Heparin prevents antiphospholipid antibody–induced fetal loss by inhibiting complement activation (2004, background): “Using a mouse model of APS induced by passive transfer of human aPL antibodies, we previously showed that complement activation is essential and causative in pregnancy loss and fetal growth restrictio”