379: Donor class I peptide immunization affects the induction but not maintenance phase of tolerance

Abstract

patient sera, 14.9% vs 2.1% control for the Mab), a reduction in platelet counts, and macroscopic blood cell agglutination. This effect was not produced by the control IgM Mab.Depletion of AVA’s from patient sera with vimentin-coated agarose beads or addition of recombinant vimentin to the blood mixture, abrogated these effects. Flow cytometry demonstrated that AVA do not bind to resting platelets in whole blood but they bind to approximately 10% of neutrophils. Binding of AVA to neutrophils resulted in complement dependent cytolysis (50%) and nuclear condensation. Supernatant derived from AVA activated neutrophils, transferred to fresh purified plalelets, caused platelet activation as measured by generation of platelet microparticles. Experiments performed in the presence of CV-6209, a PAF receptor inhibitor, prevented blood cell agglutination and platelet depletion, suggesting that PAF is one of the mediators released from AVA activated neutrophils. Conclusions: We propose a novel pathogenic mechanism whereby AVA may contribute to atherogenesis and thrombosis.