Mechanisms of autoantibody-mediated pathological thrombosis in the mouse model with antiphospholipid symdrome

The primary aims of this study are to identify epitopes recognized by antiphospholipid monolconalautoantibodies established from (NZW X BXSB) fi - D21 - D2 mice with antiphospholipid syndrome （APS）and clarify mechanisms of antibody-mediated pathological thrombosis. In addition，我们examined the platelet-membrane flip-flop translocates phosphatidylserine (PS) or cardiolipin （CL）in cells from the inside to outside in patients with APS or health controls. Identification ofepitopes recognized by antiphospholipid monolconal autoantibodies (aPL)：In this study，we succeeded to establish six monoclonal antibodies (mAb) against cardiolipin (CL) derived from (NZWX BXSB) F - 2 mice with APS. Of the 6 mAb against CL，2 clones recognized β D22 β D2 -glycoprotein I (β 2gpi)，还有这两个clones cross-reacted with the oxidative form of low-density lipoproteins （ox-LDL）。β2 gpi,也知道作为complement control protein (CCP) consists of five consensus repeat domainsa plasma glycop…更多rotein with anticoagulant activity. To identify the epitope on β 2gpi recognized by aCL，我们established five deletion mutants of β 2gpi lacking each of consensus repeat domains. .Interestingly, mAb failed to bind to all of five mutants，suggesting these mAb recognize the conformational epitopes consist of five consensus repeatdomains.Analysis of the membrane flip-flop of platelets derived from patients with APS：已已知的结合phospholipid-binding protein (PBP) such as β 2gpi or annexin Vto phospholipids (especially, PS or CL) translocated to the outside of platelet membrane，这些phospholipids are usually located at the inside leaf .这些phospholipids are usually located at the inside leafof the bilayer membrane in an intact platelet. We examined the membrane flip-flop of plateletsderived from APS patient or healthy controls in the presence of some agonists. Slightly increasedmembrane flip-flop was found in patients with APS compared with controls. suggesting that aCL/β 2gpicomplexes may contribute to platelet activation through Fc receptors. Less

The primary aims of this study are to identify epitopes recognized by antiphospholipid monolconal autoantibodies established from (NZW X BXSB) FィイD21ィエD2 mice with antiphospholipid syndrome (APS), and clarify mechanisms of antibody-mediated pathological thrombosis. In addition, we examined the platelet-membrane flip-flop translocates phosphatidylserine (PS) or cardiolipin (CL) in cells from the inside to outside in patients with APS or healthy controls. Identification of epitopes recognized by antiphospholipid monolconal autoantibodies (aPL) : In this study, we succeeded to establish six monoclonal antibodies (mAb) against cardiolipin (CL) derived from (NZW X BXSB) FィイD21ィエD2 mice with APS. Of the 6 mAb against CL, 2 clones recognized βィイD22ィエD2 -glycoprotein I (β2GPI), and also these 2 clones cross-reacted with the oxidative form of low-density lipoproteins (ox-LDL). β2GPI, also known as the complement control protein (CCP) consists of five consensus repeat domains, is a plasma glycop … More rotein with anticoagulant activity. To identify the epitope on β2GPI recognized by aCL, we established five deletion mutants of β2GPI lacking each of consensus repeat domains. Interestingly, mAb failed to bind to all of five mutants, suggesting that these mAb recognize the conformational epitopes consist of five consensus repeat domains.Analysis of the membrane flip-flop of platelets derived from patients with APS : It has been known that the binding of phospholipid-binding protein (PBP) such as β2GPI or annexin V to phospholipids (especially, PS or CL) translocated to the outside of platelet membrane, is important for aPL-mediated thrombosis. These phospholipids are usually located at the inside leaf of the bilayer membrane in an intact platelet. We examined the membrane flip-flop of platelets derived from APS patient or healthy controls in the presence of some agonists. Slightly increased membrane flip-flop was found in patients with APS compared with controls. suggesting that aCL/β2GPI complexes may contribute to platelet activation through Fc receptors. Less