β(2)GP1, Anti-β(2)GP1 Antibodies and Platelets: Key Players in the Antiphospholipid Syndrome

Anti-beta 2 glycoprotein 1 (anti-β(2)GP1) antibodies are commonly found in patients with autoimmune diseases such as the antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE). Their presence is highly associated with increased risk of vascular thrombosis and/or recurrent pregnancy-related complications. Although they are a subtype of anti-phospholipid (APL) antibody, anti-β(2)GP1 antibodies form complexes with β(2)GP1 before binding to different receptors associated with anionic phospholipids on structures such as platelets and endothelial cells. β(2)GP1 consists of five short consensus repeat termed “sushi” domains. It has three interchangeable conformations with a cryptic epitope at domain 1 within the molecule. Anti-β(2)GP1 antibodies against this cryptic epitope are referred to as ‘type A’ antibodies, and have been suggested to be more strongly associated with both vascular and obstetric complications. In contrast, ‘type B’ antibodies, directed against other domains of β(2)GP1, are more likely to be benign antibodies found in asymptomatic patients and healthy individuals. Although the interactions between anti-β(2)GP1 antibodies, β(2)GP1, and platelets have been investigated, the actual targeted metabolic pathway(s) and/or receptor(s) involved remain to be clearly elucidated. This review will discuss the current understanding of the interaction between anti-β(2)GP1 antibodies and β(2)GP1, with platelet receptors and associated signalling pathways.