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Tomonori Izumi, Mary L. Pound, Zuowei Su, G. Michael Iverson, Thomas L. Ortel
Anti-2-glycoprotein I Antibody-mediated Inhibition of Activated Protein C Requires Binding of 2-glycoprotein I to Phospholipids
To clarify the role(s) of anti-2 GPI antibodies on thrombosis in anti-phospholipid antibody syndromes (APS), the effect of IgG from three patients on activated protein C (APC) was investigated using phospholipid vesicles and purified proteins. Two of the total IgG inhibited APC activity in the presence of 2GPI, whereas the third IgG did not. In addition, one IgG inhibited APC activity without 2GPI. Anti-2GPI IgG from the two inhibitory IgG preparations inhibited APC activity only in the presence of 2GPI. Inhibition was suppressed partially by excess APC and almost completely by excess phospholipid vesicles. Cleaved 2GPI, a non-phospholipid-binding form, did not support inhibitory activity, even though the anti-2GPI IgG bound to the cleaved molecule. This study confirms that anti-2GPI antibodies from APS patients inhibit APC activity, and demonstrates the requirement of phospholipid binding of 2GPI for expression of the inhibitory activity of these antibodies.
Thrombosis and Haemostasis, Schattauer
Print ISSN: 0340-6245
Volume: 88, 01/2002
Pages: 620 - 626