β₂-Glycoprotein I: structure, mechanisms of autoantibody recognition, and polymorphisms

Identified in the 1990s as the primary target of antiphospholipid antibodies (aPL) in antiphospholipid syndrome (APS), β2-glycoprotein I (β2GPI) remains a central focus in hematology and immunology. Anti-β2GPI antibodies are important not only for diagnosing APS but also play a key role in causing thrombosis and pregnancy complications in these patients. Elucidating the molecular basis of antibody-β2GPI interactions is therefore critical for advancing APS research and has broad implications for understanding related thrombotic autoimmune disorders. In this review, we summarize recent progress on the structural biology of β2GPI, discuss mechanisms of autoantibody recognition, and provide an update on genetic polymorphisms. By resolving longstanding controversies and uncovering new regulatory principles, structural insights are paving the way for targeted approaches aimed at selectively neutralizing pathogenic autoantibodies without broadly impairing coagulation or immune function, offering promising paths toward transformative APS therapies.