Understanding the Structure of β₂-Glycoprotein I: New Insights and Future Paths for Antiphospholipid Syndrome

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by recurrent life-threatening blood clots and pregnancy complications in individuals with antiphospholipid antibodies. Among these antibodies, those targeting the plasma glycoprotein β₂-glycoprotein I (β₂GPI) are particularly important clinically. Despite extensive research, ongoing controversies persist regarding the structure of β₂GPI, which has substantial implications for understanding autoantibody reactivity and APS development. This article critically examines recent advancements in the structural biology of β₂GPI and its relevance to the recognition of antiphospholipid antibodies. Additionally, it introduces a new structure-based theory to explain how autoantibodies interact with β₂GPI and functional consequence of this interaction. Finally, it identifies potential areas for future research that could enhance approaches to diagnosing and treating APS.