Spholipid syndrome 
(APS), defined by thrombosis and recurrent pregnancy loss {in
Spholipid syndrome (APS), defined by thrombosis and recurrent pregnancy loss within the presence of antiphospholipid (aPL) antibodies, is normally treated with anticoagulation. Due to the fact complement activation is essential and causative in aPL antibody-induced fetal injury, we hypothesized that heparin protects mice from fetal loss in APS by stopping complement activation on trophoblasts and that anticoagulation, per se, just isn’t sufficient to stop miscarriage. We applied a murine model of APS in which pregnant mice are injected with human IgG-containing aPL antibodies (aPL-IgG) or IgG from wholesome men and women (NH-IgG). Passive transfer of aPL-IgG triggered a. frequency of fetal resorption (Pversus NH-IgG) and therapy with either unfractionated heparin (UFH) (U or U subcutaneously twice day-to-day) or low molecular weight heparin (LMWH) (enoxaparin) lowered the frequency of fetal resorption to that of mice treated with NH-IgG: UFH + aPL, UFH + aPL LMWH + aPL, NH-IgG,. (Pversus aPL). Even within the absence of detectable anticoagulation, as in mice treated with U UFH, heparins prevented aPL-induced pregnancy loss and inhibited systemic complement activation evidenced by generation of CadesArg (aPL, ngml; UFHU + aPL, ; LMWH + aPL, ; NH-IgG Pversus NH-IgG). Heparin restricted C deposition in deciduas of mice treated with aPL. Neither fondaparinux nor hirudin inhibited the generation of complement split goods or prevented pregnancy loss, despite anticoagulation levels comparable with heparin, indicating that anticoagulation is insufficient therapy for APS-associated miscarriage. We assessed the effects of anticoagulants on complement activation in vitro employing BeWo cells, trophoblast-like cells with externalized phosphatidylserine recognized by aPL. APL-opsonized BeWo cells cultured with mouse serum activated complement, evidenced by increased surface-bound C fragments (detected as C staining by FACS) and generation of soluble CadesArg in supernatants. In the presence of UFH or LMWH, even so, complement activation was totally inhibited (CadesArg ngml: aPL, ; UFH + aPL, ; LMWH + aPL, ; C-positive BeWo cells by FACS: aPL, ; aPL + UFH, ; LMWH + aPL, ; Pversus aPL). In contrast, neither fondaparinux nor hirudin inhibited complement activation in vitro. In conclusion, heparins inhibit complement activation in vitro and in vivo. Heparins may possibly stop obstetrical complications in APS by blocking activation of complement induced by aPL targeted to deciduas — not by preventing placental thrombosis. These findings clarify how subanticoagulant doses of heparin can limit antibody-mediated tissue injury.Age years DegradationAGE levelsOA MedChemExpress PP58 Incidence Age years AGE levelsG Girardi, P Redecha, J Salmon Hospital for Particular Surgery, Weill Healthcare College, Cornell University, New York, USA Arthritis Res Ther , (Suppl): (DOI .ar)AGE levelsStiffness PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/26622343?dopt=Abstract Brittleness AGE levels (P.) Inhibition of complement activation: a novel mechanism for the protective effects of heparin in antiphospholipid antibody-induced pregnancy lossFigureHypothesis of how advanced glycation endproduct (AGE)-related accumulation of AGEs could predispose for the improvement of osteoarthritis (OA).Session B Osteoarthritis: pathogenesisgrowth elements (P.) Sophisticated glycation endproducts in the development of osteoarthritisJ DeGroot, RA Bank, JWJ Bijlsma, JM TeKoppele, N Verzijl, FPJG Lafeber Division of Biomedical Research, TNO Pharma, Leiden, The Netherlands; Department of Rheumatology and Clinical Immunology.