Avtor/Urednik		Praprotnik, Sonja; Blank, Miri; Levy, Yair; Sigal, Tavor; Boffa, Marie-Claire; Weksler, Babette; Eldor, Amiram; Shoenfeld, Yehuda
Naslov		Anti-endothelial cell antibodies from patients with thrombotic thrombocytopenic purpura specifically activate small vessel endothelial cells
Tip		članek
Vir		Int Immunol
Vol. in št.		Letnik 13, št. 2
Leto izdaje		2001
Obseg		str. 203-10
Jezik		eng
Abstrakt		Thrombotic thrombocytopenic purpura (TTP) is an uncommon disease of an unknown etiology, characterized by consumptive thrombocytopenia, microangiopathic hemolytic anemia, fever and acute thrombotic complications, especially within the cerebral circulation. Although anti-endothelial cell antibodies (AECA) have occasionally been shown to be present in TTP, their role in the pathogenesis of the disease has never been ascertained. In the current study we demonstrated the pathogenic activity of affinity-purified anti-endothelial cell F(ab)(2) antibodies (AECA/TTP) from four consecutive patients with active TTP. These AECA/TTP bound to and activated only microvascular endothelial cells (EC) and not large vessel EC. The specificity of AECA/TTP binding to microvascular EC was confirmed by competition assay employing membranes derived from small and large vessels EC. Activation included enhanced IL-6 and von Willebrand factor release from the EC followed by increased expression of adhesion molecules P-selectin, E-selectin and vascular cell adhesion molecule-1 on the EC, as evaluated by ELISA. Increased expression of adhesion molecules was followed by an increase in monocyte adhesion to EC. The level of soluble thrombomodulin (TM) also increased in the culture medium of activated microvascular EC upon exposure to AECA/TTP antibodies and was directly correlated to a decrease in cell-associated TM. Our data suggest that AECA/TTP directed against microvascular EC could play a pathogenic role in the development of endothelial injury in TTP that leads to thrombosis.
Deskriptorji		PURPURA, THROMBOTIC THROMBOCYTOPENIC AUTOANTIBODIES ENDOTHELIUM, VASCULAR PLASMAPHERESIS IGG INTERLEUKIN-6 CELL LINE IMMUNOGLOBULINS, FAB VON WILLEBRAND FACTOR VASCULAR CELL ADHESION MOLECULE-1