ANTIENDOTHELIAL CELL ANTIBODY-BINDING MAKES NEGATIVELY CHARGED PHOSPHOLIPIDS ACCESSIBLE TO ANTIPHOSPHOLIPID ANTIBODIES

Objective. Anti-endothelial cell autoantibodies (AECA) are often assoc iated with antibodies to anionic phospholipids (PL), such as phosphati dylserine (PS), Yet, beta(2)-glycoprotein I (beta(2)GPI)-dependent ant i-FL antibodies (aPL) do not have access to their target antigens on t he membrane of endothelial cells (EC), Given that AECA are capable of exposing PS and, thereby, initiating apoptosis, we explored the relati onships between AECA, beta(2)GFI, and aPL on the surface of EC. Method s. Human EC,were incubated with mouse AECA monoclonal antibodies, and the translocation of PS was established through the binding of annexin V, which binds specifically to PS, A rabbit anti-beta(2)GPI antibody and biotin-conjugated F(ab')(2) aPL derived from 3 patients were also used to detect beta(2)GPI on the cells. Results. Twenty percent to 36% of the cells expressed anionic PL following incubation with AECA, as revealed by the binding of annexin V and beta(2)GPI, The proportion of anionic PL-expressing EC (up to 90%) correlated with the period of in cubation of EC with AECA and depended on the dose of AECA, Bound aPL r esided exclusively within the AECA-positive EC population, Conclusion, Based on our findings, AECA may be pathogenic. Some of them may even have the potential to induce production of aPL.