Indications for a protective function of beta2-glycoprotein I in thrombotic thrombocytopenic purpura

Du, Vivian X; van Os, Gwen; Kremer Hovinga, Johanna A; Dienava-Verdoold, Ilze; Wollersheim, Jacques; Ruggeri, Zaverio M; Fijnheer, Rob; de Groot, Philip G; de Laat, Bas (2012). Indications for a protective function of beta2-glycoprotein I in thrombotic thrombocytopenic purpura. British journal of haematology, 159(1), pp. 94-103. Oxford: Wiley-Blackwell 10.1111/bjh.12004

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Haematology and Central Haematological Laboratory

UniBE Contributor:

Kremer Hovinga, Johanna Anna

ISSN:

0007-1048

Publisher:

Wiley-Blackwell

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:28

Last Modified:

17 Mar 2015 21:12

Publisher DOI:

10.1111/bjh.12004

PubMed ID:

22881339

Web of Science ID:

000308871500013

URI:

https://boris.unibe.ch/id/eprint/10373 (FactScience: 216245)

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