Erschienen in:
01.09.2004 | Poster presentation
Inhibition of complement activation: a novel mechanism for the protective effects of heparin in antiphospholipid antibody-induced pregnancy loss
verfasst von:
G Girardi, P Redecha, J Salmon
Erschienen in:
Arthritis Research & Therapy
|
Sonderheft 3/2004
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Excerpt
The antiphospholipid syndrome (APS), defined by thrombosis and recurrent pregnancy loss in the presence of antiphospholipid (aPL) antibodies, is generally treated with anticoagulation. Because complement activation is essential and causative in aPL antibody-induced fetal injury, we hypothesized that heparin protects mice from fetal loss in APS by preventing complement activation on trophoblasts and that anticoagulation, per se, is not sufficient to prevent miscarriage. We used a murine model of APS in which pregnant mice are injected with human IgG-containing aPL antibodies (aPL-IgG) or IgG from healthy individuals (NH-IgG). Passive transfer of aPL-IgG caused a 43.3 ± 3.5% frequency of fetal resorption (P < 0.001 versus NH-IgG) and treatment with either unfractionated heparin (UFH) (10 U or 20 U subcutaneously twice daily) or low molecular weight heparin (LMWH) (enoxaparin) reduced the frequency of fetal resorption to that of mice treated with NH-IgG: UFH10 + aPL, 9.6 ± 3.2; UFH20 + aPL 10.4 ± 2.1; LMWH + aPL, 11.8 ± 2.8; NH-IgG, 10.5 ± 2.5% (P < 0.01 versus aPL). Even in the absence of detectable anticoagulation, as in mice treated with 10 U UFH, heparins prevented aPL-induced pregnancy loss and inhibited systemic complement activation evidenced by generation of C3adesArg (aPL, 1212 ± 101* ng/ml; UFH10U + aPL, 178 ± 25; LMWH + aPL, 180 ± 15; NH-IgG, 215 ± 381, * P < 0.05 versus NH-IgG). Heparin limited C3 deposition in deciduas of mice treated with aPL. Neither fondaparinux nor hirudin inhibited the generation of complement split products or prevented pregnancy loss, despite anticoagulation levels comparable with heparin, indicating that anticoagulation is insufficient therapy for APS-associated miscarriage. …