title: A potential anti-coagulant role of complement factor H.
abstract: Anti-phospholipid syndrome (APS) is a complex autoimmune disease, associated with recurrent venous and arterial thrombosis in various tissues. APS is associated with specific antibodies against plasma beta-2 glycoprotein 1 (β2-GP1), and these antibodies react with β2-GP1 bound to negatively charged phospholipids (e.g. cardiolipin) on cell membranes. Some APS patients also have autoantibodies to complement factor H (FH), a homologue of β2-GP1, which also binds to anionic phospholipids. β2-GP1 has earlier been shown to inhibit the intrinsic (contact) activated blood coagulation pathway, promoted by anionic phospholipids. Here we examine whether FH could have similar anti-thrombotic properties. In vitro experiments with surface-bound phospholipids and human plasma, in the presence of FH, confirm this hitherto unreported property of FH.
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK; Centre for Infection, Immunity and Disease Mechanisms, Biosciences, Heinz Wolff Building, Brunel University, London UB8 3PH, UK.
authors.forename: Janez
authors.initials: J
authors.lastname: Ferluga
authors.affiliation: Centre for Infection, Immunity and Disease Mechanisms, Biosciences, Heinz Wolff Building, Brunel University, London UB8 3PH, UK.
authors.forename: Uday
authors.initials: U
authors.lastname: Kishore
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK; Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK. Electronic address: bob.sim@bioch.ox.ac.uk.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Sim
mesh_terms: D017152:Antibodies, Antiphospholipid / Q000276:immunology*; D000925:Anticoagulants / Q000494:pharmacology; D016736:Antiphospholipid Syndrome / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D001777:Blood Coagulation / Q000187:drug effects / Q000502:physiology*; D002308:Cardiolipins / Q000276:immunology; D017242:Complement Factor H / Q000276:immunology / Q000494:pharmacology / Q000502:physiology; D005174:Factor XII / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D010712:Phosphatidic Acids / Q000276:immunology; D010718:Phosphatidylserines / Q000276:immunology; D010743:Phospholipids; D013927:Thrombosis / Q000276:immunology; D053482:beta 2-Glycoprotein I / Q000276:immunology*
chemical_list: D017152:Antibodies, Antiphospholipid; D000925:Anticoagulants; D001323:Autoantibodies; C493495:CFH protein, human; D002308:Cardiolipins; D010712:Phosphatidic Acids; D010718:Phosphatidylserines; D010743:Phospholipids; D053482:beta 2-Glycoprotein I; D017242:Complement Factor H; D005174:Factor XII
keywords: Factor H; anti-phospholipid syndrome; coagulation; complement