Evidence for Anticoagulant Activity and β2 -GPI Accumulation in Late Endosomes of Endothelial Cells Induced by Anti-LBPA Antibodies

This investigation was undertaken to test whether anti-LBPA anti-bodies and IgG from patients with APS interfere with intracellular β2 GPI distribution in EAhy926 endothelial cells and with the coagula-tion system. Cell incubation with anti-LBPA MoAb or with patients’ IgG resulted in antibody binding to late endosomes and caused β2 GPI redistribution and accumulation within perinuclear vesicular structures reminiscent of late endosomes. This finding suggests that aPl may contribute to the pathogenic mechanisms of APS by modifying the intracellular traffic of proteins, by interactions between aPl and LBPA, β2 GPI and/or LBPA-β2 GPI complexes. The anticoagulant activity of anti-LBPA MoAb was analyzed in a sensitized activated partial throm-boplastin time (aPTT) system and in a dilute Russell’s viper venom time (dRVVT). A significant, concentration-dependent effect of the antibody on both aPTT and dRVVT prolongation was found. These observations suggest that LBPA is an important lipid target for aPl with potential functional implications for the immunopathogenesis of APS.