EFFECT OF BETA-2GLYCOPROTEIN-I AND HUMAN MONOCLONAL ANTICARDIOLIPIN ANTIBODY ON THE PROTEIN S C4B-BINDING PROTEIN SYSTEM/

The effect of beta 2glycoprotein I (beta 2GPI) and human monoclonal an ticardiolipin antibody (aCL) on the protein S/C4b-binding protein (C4B P) system was evaluated. The binding of C4BP to protein S was assessed by ELISA in the presence of beta 2GPI with/without human monoclonal a CL. beta 2GPI downregulated the binding between S and C4BP significant ly. Human monoclonal aCL abolished the beta 2GPI inhibitory effect in a calcium (Ca++) independent fashion. In separate experiments, the rea ctivity of aCL towards protein S in the presence or absence of beta 2G PI and cardiolipin was investigated. Monoclonal aCL bound to protein S only in the presence of a combination of beta 2GPI and cardiolipin. T his binding was Ca++ dependent. These findings suggest that human mono clonal aCL increases the affinity of C4BP for protein S, and that prot ein S may represent one of the targets for aCL when combined with beta 2GPI and cardiolipin. Both issues may explain acquired free protein S deficiency and the attendant risk of thrombosis in patients with aCL.