The β ₂-Glycoprotein I/HLA–DR Complex As a Major Autoantibody Target in Obstetric Antiphospholipid Syndrome

Objective: The clinical manifestations of antiphospholipid syndrome (APS) include vascular thrombosis and pregnancy morbidity as well as recurrent pregnancy loss (RPL). However, in more than half of patients with RPL, the cause is never determined. Recently, β₂-glycoprotein I (β₂GPI) complexed with HLA class II molecules (β₂GPI/HLA-DR) was found to be a major autoantibody target in APS. The present study was undertaken to assess the serum levels of autoantibodies against the β₂GPI/HLA II complex as a potential risk factor for RPL in women. Methods: Serum levels of antiphospholipid antibodies (aPLs), including IgG/IgM anticardiolipin antibodies, IgG/IgM anti–β₂GPI antibodies, and lupus anticoagulant as well as anti-β₂GPI/HLA–DR antibodies, were measured in 227 women with RPL. In this prospective, multicenter, cross-sectional study, women with RPL and their partners underwent HLA–DR immunotyping and analysis to identify potential causes and risk factors associated with RPL. The normal range for anti-β₂GPI/HLA–DR antibody levels was determined using serum samples obtained from a control population of female subjects (208 women of childbearing potential). Results: Of the 227 women with RPL, aPL antibodies were detected in 19.8%, and 52 (22.9%) tested positive for anti-β₂GPI/HLA–DR antibodies. Among the 227 women, 121 (53.3%) had no risk factors for RPL, and among these women with unexplained RPL, 24 (19.8%) were positive for anti-β₂GPI/HLA–DR antibodies. Of the 112 women who had clinical symptoms of APS but did not have levels of aPLs that met the diagnostic criteria for APS, 21 (18.8%) were positive for anti-β₂GPI/HLA–DR antibodies. Conclusion: The anti-β₂GPI/HLA–DR antibody is frequently associated with RPL. Detection of these autoantibodies is useful in understanding the pathogenesis of RPL. Our findings may provide potential new therapeutic strategies for addressing RPL in patients with obstetric APS.