Anti-beta(2)-glycoprotein I antibody-mediated inhibition of activated protein C requires binding of beta(2)-glycoprotein I to phospholipids.
To clarify the role(s) of anti-beta(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 beta(2)GPI, whereas the third IgG did not. In addition, one IgG inhibited APC activity without beta(2)GPI. Anti-beta(2)GPI IgG from the two inhibitory IgG preparations inhibited APC activity only in the presence of beta(2)GPI. Inhibition was suppressed partially by excess APC and almost completely by excess phospholipid vesicles. Cleaved beta(2)GPI, a non-phospholipid-binding form, did not support inhibitory activity, even though the anti-beta(2)GPI IgG bound to the cleaved molecule. This study confirms that anti-beta(2)GPI antibodies from APS patients inhibit APC activity, and demonstrates the requirement of phospholipid binding of beta(2)GPI for expression of the inhibitory activity of these antibodies.
Duke Scholars
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Related Subject Headings
- beta 2-Glycoprotein I
- Thromboembolism
- Protein C
- Protein Binding
- Phospholipids
- Membranes, Artificial
- Immunoglobulin G
- Humans
- Glycoproteins
- Factor Va
Citation
Published In
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- beta 2-Glycoprotein I
- Thromboembolism
- Protein C
- Protein Binding
- Phospholipids
- Membranes, Artificial
- Immunoglobulin G
- Humans
- Glycoproteins
- Factor Va