Self-interaction of soluble and surface-bound β₂-glycoprotein I and its enhancement by lupus anticoagulants

Antiphospholipid antibodies found in antiphospholipid syndrome are autoantibodies to phospholipid-binding proteins, such as β₂-glycoprotein I (β₂GPI). We have previously reported that among these antibodies, the so-called lupus anticoagulants (LAs) augment β₂GPI binding to the phospholipid membrane surface, which is associated with the pathological action of LAs. However, the molecular mechanisms underlying this augmentation are uncertain. Here we show that β₂GPI, which is monomeric in solution, self-interacts at the interface of soluble and surface-bound molecules. In addition, this self-interaction is enhanced by LA-positive, but not LA-negative, anti-β₂GPI monoclonal antibodies. This study suggests that β₂GPI self-interaction upon surface binding could be involved in the LA-induced potentiation of β₂GPI binding to the phospholipid surface. Structured summary: MINT-6743767:beta2GPI (uniprotkb:P02749) binds (MI:0407) to beta2GPI (uniprotkb:P02749) by surface plasmon resonance (MI:0107)MINT-6743776:beta2GPI (uniprotkb:P02749) binds (MI:0407) to beta2GPI (uniprotkb:P02749) by saturation binding (MI:0440).