Anti-β2-glycoprotein I antibodies recognizing platelet factor 4-heparin complex in antiphospholipid syndrome in patient substantiated with mouse model

The antiphospholipid syndrome is defined by the presence of antiphospholipid antibodies associated with arterial and/or venous thrombosis, and recurrent abortion accompanied often by thrombocytopenia. These antibodies are heterogeneous and react against phospholipid-binding proteins such as beta(2)-glycoprotein I (beta(2)GPI) and prothrombin. The recognition of anti-beta(2)-glycoprotein I (anti-beta(2)GPI) by platelet factor 4-heparin complex (PF4-Hc) has been previously evoked and partially confirmed by the present inhibition studies. Further, the anti-beta(2)-glycoprotein I antibodies were purified from a patient with primary antiphospholipid syndrome using Affi-gel(R)-10-beta(2)GPI immunoaffinity chromatography. The purified anti-beta(2)GPI IgM as well as patient serum equally recognized PF4-Hc in ELISA mode. In order to substantiate this data and to better understand we studied an animal model using mouse active immunization with the purified human anti-beta(2)GPI. The mice showed a significant decrease in their platelet count. In addition the ELISA responses of the immunized mice sera were positive against both beta(2)GPI and PF4-Hc, substantiating the double recognition. Despite many previous reported animal model studies, this is the first time we have shown the specific recognition of anti-beta(2)GPI antibodies by PF4-Hc, the results in the induced mice correlating the data observed with some patients. Copyright (C) 2003 John Wiley Sons, Ltd.