Antiphospholipid cofactor.

A plasma protein is required as a cofactor for the binding of antiphospholipid antibodies to phospholipids. This protein has been identified as beta 2-glycoprotein I, an apolipoprotein that binds to negatively charged phospholipids and is a natural inhibitor of the coagulation cascade. It is not certain whether antiphospholipid antibodies bind to beta 2-glycoprotein I alone, to beta 2-glycoprotein I-phospholipid complex, or to a phospholipid epitope modified by beta 2-glycoprotein I. We used isolated beta 2-glycoprotein I and purified IgG and IgM antiphospholipid antibodies from serum or plasma of patients with the antiphospholipid syndrome to study the relation between antiphospholipid antibodies and beta 2-glycoprotein I in enzyme-linked immunosorbent assays. IgG antiphospholipid antibodies did not bind to beta 2-glycoprotein I when it was used as an antigen on the assay plate. The binding of IgG and IgM antiphospholipid antibodies to phospholipid was enhanced when beta 2-glycoprotein I was added to the phospholipid antigens either before or together with the antiphospholipid antibodies. The degree of enhancement varied across patients. IgM antiphospholipid antibodies required less cofactor for binding to phospholipid antigens. These results confirm the requirement of beta 2-glycoprotein I as a cofactor for the binding of autoimmune antiphospholipid antibodies to phospholipids.