REACTIVITY PATTERNS OF ANTIPHOSPHOLIPID ANTIBODIES AND ENDOTHELIAL-CELLS - EFFECT OF ANTIENDOTHELIAL ANTIBODIES ON CELL-MIGRATION

Antiphospholipid syndrome (APS) is characterized by the presence of a heterogenous class of antibodies directed against phospholipids and as sociated with high occurrence of thrombotic complications. Antiendothe lial cell antibodies (AECAs) have been identified in various autoimmun e disorders including APS, but their reactivity patterns remain unclea r. We used eluted endothelial membrane-bound antibodies (EC eluates) t o investigate possible cross-reactivity of AECAs and their pathogenic effects on endothelial cell integrity. The heterogenous and nonspecifi c nature of AECAs was confirmed by our finding that they cross-react w ith fibroblasts and platelets and bind to cardiolipin. In addition, pl atelet-bound antibodies from sera of patients with APS reacted with en dothelial cells. A dose-dependent binding of human monoclonal anticard iolipin antibody was demonstrated, but this antibody did not compete w ith AECAs in Pc eluates, indicating that only small portion of AECAs a re directed against cardiolipin. Although sera from APS patients prolo nged coagulation tests, Pc eluates did not affect coagulation, suggest ing that AECAs may belong to antiphospholipid antibodies subsets that does not interfere with coagulation. Vascular damage is a common featu re of autoimmune disorders associated with AECAs. Possible effects of AECAs on vascular perturbance were investigated by cytotoxicity, attac hment, and migration assays. Although AECAs were not shown to be cytot oxic or to affect cell attachment, sera from APS patients caused reduc ed cellular migration (by 30%), and EC eluates caused even more signif icant inhibition (by 50%). These findings suggest possible interferenc e of AECAs in vascular repair mechanisms and provide an explanation fo r the thrombotic complications frequently seen in APS patients.