ISOLATION AND PURIFICATION OF ANTICARDIOLIPIN ANTIBODY FROM PLASMA OFA PATIENT WITH ANTIPHOSPHOLIPID SYNDROME - INDUCED GENERATION OF PLATELET THROMBOXANE A(2) SYNTHESIS

Antiphospholipid antibodies, particularly anticardiolipin antibodies ( aCL) are autoantibodies frequently detected in the serum of patients w ith systemic lupus erythematosus (SLE) and the primary antiphospholipi d antibody syndrome (PAPS). These patients commonly suffer from thromb osis, recurrent fetal loss and thrombocytopenia. Since platelet aggreg ation is pivotal in the genesis of thrombosis, we tested the hypothesi s that perturbation of platelet membrane by aCL/beta(2)-glycoprotein ( aCL/beta(2)GP) complex could trigger the biosynthesis of TXA(2), a pro aggregatory metabolite of AA. The preincubation of C-14-arachidonic ac id (C-14-AA)-labeled platelet pellets (C-14-PP) from normal individual s with aCL alone followed by incubation with thrombin, resulted in a m oderate increase in platelet thromboxane B-2 (C-14-TXB(2)) biosynthesi s when compared to controls (without aCL). Similar incubations with be ta(2)GP-I alone resulted in negligible C-14-TXB(2) biosynthesis. In co ntrast, the preincubations of normal C-14-PP with aCL/beta(2)GP-I comp lex resulted in marked thrombin-induced TXB(2) biosynthesis, underscor ing the requirement of beta(2)GP-I in aCL-induced platelet TXB(2) bios ynthesis. Taken together, these results are consistent with the view t hat aCL/beta(2)GP-I platelet interactions do play a role, at least in part, in platelet hyperactivity and thrombosis in antiphospholipid ant ibody syndrome.