Some antiphospholipid antibodies recognize conformational epitopes shared by β2‐glycoprotein I and the homologous catalytic domains of several serine proteases

Abstract

Objective To test the hypothesis that some antiphospholipid antibodies (aPL) in patients with the antiphospholipid syndrome (APS) recognize a conformational epitope shared by β₂‐glycoprotein I (β₂GPI; the major autoantigen for the antiphospholipid antibodies) and the homologous catalytic domains of several serine proteases (such as thrombin, activated protein C [APC], and plasmin) involved in hemostasis. Methods We generated 4 new IgG monoclonal aPL (2 screened against β₂GPI, 1 against thrombin, and 1 against protein C) from 2 APS patients. The monoclonal antibodies (mAb) were analyzed for binding to β₂GPI, thrombin, APC, and plasmin, as well as for anticardiolipin antibody (aCL) activity. To demonstrate a shared epitope between β₂GPI and a serine protease, 1 mAb was studied by cross‐inhibition analysis. Results Both of the IgG anti‐β₂GPI mAb bound to thrombin, APC, and plasmin. On the other hand, the 1 anti‐thrombin mAb and the 1 anti–protein C mAb also bound to β₂GPI. Moreover, the binding of 1 cross‐reactive mAb to β₂GPI was inhibited by α‐thrombin (which contains only the catalytic domain of thrombin). All 4 mAb displayed aCL activity. Conclusion Taken together with the findings that some aCL bind to several serine proteases that participate in hemostasis and share homologous catalytic domains, these data demonstrate that some aCL in APS patients recognize one or more conformational epitopes shared by β₂GPI and the catalytic domains of disease‐relevant serine proteases.