The association between anti-phosphatidylserine/prothrombin antibodies (aPS/PT) and epidermal growth factor (EGF) in patients with recurrent pregnancy loss

We previously reported that autoantibodies to factor XII (aFXII) and protein S (aPS) in patients with recurrent pregnancy loss (RPL) recognized epidermal growth factor (EGF)-like domains. These autoantibodies also recognized EGF family proteins such as EGF and heparin-binding EGF-like growth factor (HB-EGF). Unexpectedly, autoantibodies to EGF correlated strongly with anti-phosphatidylserine/prothrombin antibodies (aPS/PT) as well as aPS and aFXII. Therefore, we investigated the association between aPS/PT and EGF in patients with recurrent pregnancy loss. In immunoblotting, aPS/PT in patients with recurrent pregnancy loss recognized α-thrombin region in prothrombin. Polyclonal antibodies to recombinant human EGF recognized not F1+2 but α-thrombin region in prothrombin. Polyclonal antibodies to prothrombin and α-thrombin recognized recombinant human EGF. These findings indicate that the antigenicity of human EGF and α-thrombin which is protease domain in prothrombin is cross reactive. Autoantibodies to EGF in patients with recurrent pregnancy loss recognizing EGF-like domains in various proteins and members of the EGF family may disrupt the EGF system and inhibit uterine and placental angiogenesis essential for embryonic and fetal survival, leading to pregnancy loss. Our present study suggests that aPS/PT may have similar pathogenicity.