International Immunology, Vol. 13, No. 2, 203-210,
February 2001
© 2001 Japanese Society for Immunology
Anti-endothelial cell antibodies from patients with thrombotic thrombocytopenic purpura specifically activate small vessel endothelial cells
1 Research Unit of Autoimmune Diseases and Department Medicine B, Chaim Sheba Medical Center, Tel-Hashomer 52621, Israel
2 Clinical center, Department of Rheumatology, Vodnikova 62, 1000 Ljubljana, Slovenia
3 Institute of Hematology, Sorasky Medical Center, Tel-Aviv 54145, Israel
4 INSERM U353, Hopital Saint-Louis, 75475 Paris, France
5 Weill Medical College of Cornell University, New York, NY 10021, USA
Correspondence to: Correspondence to: Y. Shoenfeld
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.
Keywords: adhesion molecules, anti-endothelial cell antibodies, autoimmunity, endothelial cell, thrombomodulin, thrombotic thrombocytopenic purpura