Anti-β₂ glycoprotein I antibodies in complex with β₂ glycoprotein I induce platelet activation via two receptors: apolipoprotein E receptor 2' and glycoprotein I bα

Abstract

Anti-β₂ glycoprotein I (anti-β₂GP I ) antibodies are important contributors to thrombosis, especially in patients with antiphospholipid syndrome (APS). However, the mechanism by which anti-β₂GP I antibodies are involved in the pathogenesis of thrombosis is not fully understood. In this report, we investigated the role of anti-β₂GP I antibodies in complexes with β₂GP I as mediators of platelet activation, which can serve as a potential source contributing to thrombosis. We examined the involvement of the apolipoprotein E receptor 2' (apoER2') and glycoprotein I ba (GP I bα) in platelet activation induced by the anti-β₂GP I /β₂GP I complex. The interaction between the anti-β₂GP I /β₂GP I complex and platelets was examined using in vitro methods, in which the Fc portion of the antibody was immobilized using protein A coated onto a microtiter plate. Platelet activation was assessed by measuring GP II b/ III a activation and P-selectin expression and thromboxane B₂ production as well as p38 mitogen-activated protein kinase phosphorylation. Our results revealed that the anti-β₂GP I /β₂GP I complex was able to activate platelets, and this activation was inhibited by either the anti-GP I bα antibody or the apoER2' inhibitor. Results showed that the anti-β₂GP I /β₂GP I complex induced platelet activation via GP I bα and apoER2', which may then contribute to the prothrombotic tendency in APS patients.

Keywords

anti-β₂GP I /β₂GP I complex / platelet / GP I bα / apoER2' / thrombosis

References

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (No. 81270394) to Yanhong Liu. The authors would like to thank Xing Liu for providing expert technical assistance.

Compliance with ethics guidelines

Wenjing Zhang, Fei Gao, Donghe Lu, Na Sun, Xiaoxue Yin, Meili Jin, and Yanhong Liu declare that there are no financial or other relationships that might lead to a conflict of interest of the present article. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (Harbin University Institutional Review Committee, China) and with the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consent was obtained from all patients included in the study.

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