Immunoglobulin G fractions from patients with antiphospholipid antibodies cause fetal death in BALB/c mice: A model for autoimmune fetal loss

Branch, D. Ware; Dudley, Donald J.; Mitchell, Murray D.; Creighton, Kathryn A.; Abbott, Thomas M.; Hammond, Elizabeth H.; Daynes, Raymond A.

doi:10.1016/s0002-9378(11)90700-5

Cited by 319 publications

(137 citation statements)

References 19 publications

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“…The pathogenic mechanisms for antiphospholipid antibody (aPL)-induced thrombosis are incompletely understood. Passive transfer of IgG from aPL-positive sera (IgG-APS) has been found to induce fetal loss, thrombosis, and endothelial cell activation in mice, suggesting a direct pathogenic role of aPL (1)(2)(3). Complement activation is a necessary intermediary event in the pathogenesis of fetal loss associated with aPL in this model (4,5).…”

mentioning

confidence: 81%

Requirement of activation of complement C3 and C5 for antiphospholipid antibody–mediated thrombophilia

Pierangeli¹,

Girardi²,

Vega-Ostertag³

et al. 2005

Arthritis & Rheumatism

331

215

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Objective. Antiphospholipid antibodies (aPL) have been shown to induce thrombosis, activate endothelial cells, and induce fetal loss. The pathogenesis of aPLinduced thrombosis, although not completely understood, may involve platelet and endothelial cell activation as well as procoagulant effects of aPL directly on clotting pathway components. Recent studies have shown that uncontrolled complement activation leads to fetal death in aPL-treated mice. In this study, we tested the hypothesis that aPL are responsible for activation of complement, thus generating split products that induce thrombosis.Methods. To study thrombus dynamics and adhesion of leukocytes we used in vivo murine models of thrombosis and microcirculation, in which injections of aPL were used.Results. Mice deficient in complement components C3 and C5 were resistant to the enhanced thrombosis and endothelial cell activation that was induced by aPL. Furthermore, inhibition of C5 activation using anti-C5 monoclonal antibodies prevented thrombophilia induced by aPL.Conclusion. These data show that complement activation mediates 2 important effectors of aPL, induction of thrombosis and activation of endothelial cells.

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mentioning

confidence: 81%

Requirement of activation of complement C3 and C5 for antiphospholipid antibody–mediated thrombophilia

Pierangeli¹,

Girardi²,

Vega-Ostertag³

et al. 2005

Arthritis & Rheumatism

331

215

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“…Passive transfer of whole immunoglobulin fractions from aPL-positive sera has been found to induce fetal loss and growth retardation in pregnant naive mice, suggesting a direct pathogenetic role (2)(3)(4).…”

mentioning

confidence: 99%

Antiphospholipid antibodies affect trophoblast gonadotropin secretion and invasiveness by binding directly and through adhered β2-glycoprotein I

Simone

Meroni

Papa

et al. 2000

Arthritis & Rheumatism

293

179

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Objective. To investigate the in vitro ability of antiphospholipid antibodies (aPL) to bind human trophoblast cells and to affect gonadotropin secretion and invasiveness.Methods. Antiphospholipid antibody IgG from women with recurrent miscarriages, ␤ 2 -glycoprotein I (␤ 2 GPI)-independent IgG aPL human monoclonal antibody (mAb) (519), and IgM anti-␤ 2 GPI human mAb (TM1G2) were investigated for their binding to trophoblasts cultured for various amounts of time, their ability to affect invasiveness of Matrigel-coated filters, and their release of human chorionic gonadotropin (hCG).Results. Polyclonal IgG aPL, as well as mAb 519 and TM1G2, bound to trophoblasts, the highest binding being found when cells displayed the greatest amount of syncytium formation. TM1G2 binding was found to be ␤ 2 GPI dependent. Both polyclonal and monoclonal aPL, but not the controls, significantly reduced hCG release and Matrigel invasiveness.Conclusion. These findings suggest that aPL recognition of both anionic PL and adhered ␤ 2 GPI on trophoblast cell structures might represent a potential pathogenetic mechanism for defective placentation in women with the antiphospholipid syndrome.

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“…This is supported by induction of these complications in normal mice following passive transfer of aPL antibodies from APS patients 5,6 . Several mechanisms by which aPL antibodies may cause these complications have been suggested: Activation of endothelial cells and increased expression of adhesion molecules, resulting in increased adherence of platelets and monocytes to endothelial cells.…”

Section: Pathogenesismentioning

confidence: 85%

Anticardiolipin syndrome: antiphospholipid syndrome

Gharavi

2001

Clinical Medicine

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Immunoglobulin G fractions from patients with antiphospholipid antibodies cause fetal death in BALB/c mice: A model for autoimmune fetal loss

Cited by 319 publications

References 19 publications

Requirement of activation of complement C3 and C5 for antiphospholipid antibody–mediated thrombophilia

Requirement of activation of complement C3 and C5 for antiphospholipid antibody–mediated thrombophilia

Antiphospholipid antibodies affect trophoblast gonadotropin secretion and invasiveness by binding directly and through adhered β2-glycoprotein I

Anticardiolipin syndrome: antiphospholipid syndrome

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