A potential anti-coagulant role of complement factor H

Janez Ferluga; Uday Kishore; Robert B Sim

doi:10.1016/j.molimm.2014.02.012

A potential anti-coagulant role of complement factor H

Mol Immunol. 2014 Jun;59(2):188-93. doi: 10.1016/j.molimm.2014.02.012. Epub 2014 Mar 13.

Authors

Janez Ferluga¹, Uday Kishore², Robert B Sim³

Affiliations

¹ 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.
² Centre for Infection, Immunity and Disease Mechanisms, Biosciences, Heinz Wolff Building, Brunel University, London UB8 3PH, UK.
³ 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.

PMID: 24632373
DOI: 10.1016/j.molimm.2014.02.012

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.

Keywords: Factor H; anti-phospholipid syndrome; coagulation; complement.

MeSH terms

Antibodies, Antiphospholipid / immunology*
Anticoagulants / pharmacology
Antiphospholipid Syndrome / immunology
Autoantibodies / immunology
Blood Coagulation / drug effects
Blood Coagulation / physiology*
Cardiolipins / immunology
Complement Factor H / immunology
Complement Factor H / pharmacology
Complement Factor H / physiology
Factor XII / antagonists & inhibitors
Factor XII / metabolism
Humans
Phosphatidic Acids / immunology
Phosphatidylserines / immunology
Phospholipids
Thrombosis / immunology
beta 2-Glycoprotein I / immunology*

Substances

Antibodies, Antiphospholipid
Anticoagulants
Autoantibodies
CFH protein, human
Cardiolipins
Phosphatidic Acids
Phosphatidylserines
Phospholipids
beta 2-Glycoprotein I
Complement Factor H
Factor XII