The β2‐Glycoprotein I/HLA–DR Complex As a Major Autoantibody Target in Obstetric Antiphospholipid Syndrome

Abstract

Objectives The clinical manifestations of antiphospholipid syndrome (APS) include vascular thrombosis and pregnancy morbidity, including recurrent pregnancy loss (RPL). However, more than half of RPL patients never determine the cause of their RPL. Recently, β2‐glycoprotein I (β2GPI) complexed with human leukocyte antigen class II molecules (β2GPI/HLA‐II) was found to be a major autoantibody target in APS. In this study, autoantibodies against the β2GPI/HLA‐II complex were analyzed in women with RPL, which is a clinical symptom of obstetric APS. Methods Serum levels of antiphospholipid antibodies (aPL), including immunoglobulin (Ig) G/IgM anti‐cardiolipin antibody, IgG/IgM anti‐β2GPI antibody, 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 obtained from 208 fertile women used as controls. Results aPL was detected in 19.8% of women with RPL. Fifty‐two out of the 227 (22.9%) women with RPL tested positive for anti‐β2GPI/HLA‐DR antibodies, and 24 out of the 121 (19.8%) women with unexplained RPL were positive for anti‐β2GPI/HLA‐DR antibodies. Twenty‐one out of 112 (18.8%) women, who had clinical symptoms of APS but not aPL of criteria, tested positive for anti‐β2GPI/HLA‐DR antibodies. Conclusions 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 will potentially provide new therapeutic modalities for patients with obstetric APS.