Extracellular phosphatidylserine–β2-glycoprotein I complex (PS-β2GPI complex)

The extracellular phosphatidylserine–β2-glycoprotein I (PS-β2GPI) complex is a molecular assembly formed when the anionic phospholipid phosphatidylserine is exposed on the outer surface of cells during apoptosis or malignant transformation (Schroit et al., 1985). Once exposed, PS binds to the plasma protein β2-glycoprotein I, creating a stable complex that serves as a potent signaling platform (Miyakis et al., 2006). In oncology, this complex is highly prevalent in the tumor microenvironment, particularly on tumor vascular endothelial cells and tumor-derived microvesicles (He et al., 2009). It contributes to an immunosuppressive milieu by inhibiting dendritic cell maturation and promoting M2 macrophage polarization (Gerber et al., 2015). Therapeutic antibodies like bavituximab target this complex to reverse tumor-induced immunosuppression and induce antibody-dependent cellular cytotoxicity (ADCC) (He et al., 2009). Beyond cancer, the PS-β2GPI complex is the primary autoantigen in antiphospholipid syndrome (APS), where it is targeted by pathogenic autoantibodies (Giannakopoulos & Krilis, 2013). These autoantibodies trigger thrombotic events and pregnancy complications by activating endothelial cells and platelets (Miyakis et al., 2006). The complex is also involved in the entry of certain enveloped viruses into host cells, acting as a bridge for viral attachment (Soares et al., 2008). Consequently, the PS-β2GPI complex represents a critical target for both anti-tumor immunotherapy and the management of autoimmune thrombotic disorders.

Other names

Phosphatidylserine-Apolipoprotein H complexPS-APOH complexPS-beta2GPI complexPhosphatidylserine-beta-2-glycoprotein 1 complex

Bavituximab binds to the PS-β2GPI complex on tumor vessels and microvesicles, triggering immune-mediated destruction via antibody-dependent cellular cytotoxicity (ADCC) and repolarizing the tumor microenvironment from immunosuppressive to immunostimulatory (He et al., 2009; Gerber et al., 2015).