title: Indications for a protective function of beta2-glycoprotein I in thrombotic thrombocytopenic purpura.
abstract: It has been shown that β(2) -glycoprotein I (β(2) GPI) interacts with von Willebrand factor (VWF) in a glycoprotein (GP)Ib binding state. Given the presence of active VWF multimers in thrombotic thrombocytopenic purpura (TTP), we speculated that β(2) GPI might play a role in TTP. We found that β(2) GPI plasma levels were significantly lower in acute and remission TTP patients than in normal controls, showing a direct correlation with ADAMTS 13 levels and an inverse correlation with the extent of VWF activation. In vitro flow experiments demonstrated that β(2) GPI can block platelet adhesion to endothelial cell-derived VWF strings. We confirmed the direct binding of β(2) GPI to VWF by surface plasmon resonance, and determined that domain I of β(2) GPI is the binding site of VWF A1 domain. Adhesion of β(2) GPI to erythrocytes and platelets was increased in the presence of active VWF, indicating that β(2) GPI may be cleared from the circulation during TTP episodes together with blood cells. Our findings suggest that β(2) GPI may protect from the effects of hyper-functional VWF by inhibiting its interaction with platelets.
authors.affiliation: Clinical Chemistry and Haematology, University Medical Centre, Utrecht, The Netherlands.
authors.forename: Vivian X
authors.initials: VX
authors.lastname: Du
authors.forename: Gwen
authors.initials: G
authors.lastname: van Os
authors.forename: Johanna A
authors.initials: JA
authors.lastname: Kremer Hovinga
authors.forename: Ilze
authors.initials: I
authors.lastname: Dienava-Verdoold
authors.forename: Jacques
authors.initials: J
authors.lastname: Wollersheim
authors.forename: Zaverio M
authors.initials: ZM
authors.lastname: Ruggeri
authors.forename: Rob
authors.initials: R
authors.lastname: Fijnheer
authors.forename: Philip G
authors.initials: PG
authors.lastname: de Groot
authors.forename: Bas
authors.initials: B
authors.lastname: de Laat
mesh_terms: D058846:Antibodies, Monoclonal, Murine-Derived / Q000276:immunology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D002478:Cells, Cultured; D004912:Erythrocytes / Q000378:metabolism / Q000473:pathology; D057809:HEK293 Cells; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D010974:Platelet Aggregation; D011697:Purpura, Thrombotic Thrombocytopenic / Q000097:blood*; D012310:Ristocetin / Q000494:pharmacology; D053482:beta 2-Glycoprotein I / Q000037:antagonists & inhibitors / Q000097:blood* / Q000276:immunology; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D053482:beta 2-Glycoprotein I; D014841:von Willebrand Factor; D012310:Ristocetin