Anti-β2-glycoprotein I antibody-mediated inhibition of activated protein C requires binding of β2-glycoprotein I to phospholipids

To clarify the role(s) of anti-β2GPI antibodies on thrombosis in antiphospholipid 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 β2GPI, whereas the third IgG did not. In addition, one IgG inhibited APC activity without β2GPI. Anti-β2GPI IgG from the two inhibitory IgG preparations inhibited APC activity only in the presence of β2GPI. Inhibition was suppressed partially by excess APC and almost completely by excess phospholipid vesicles. Cleaved β2GPI, a non-phospholipid-binding form, did not support inhibitory activity, even though the anti-β2GPI IgG bound to the cleaved molecule. This study confirms that anti-β2GPI antibodies from APS patients inhibit APC activity, and demonstrates the requirement of phospholipid binding of β2GPI for expression of the inhibitory activity of these antibodies.

Duke Scholars

Author Thomas Lee Ortel Medicine, Hematology