Anti-beta 2-glycoprotein I antibodies and anti-endothelial cell antibodies induce tissue factor in endothelial cells.
Anti-beta 2-glycoprotein I antibodies bind to endothelial cells through beta 2-GPI. The antibodies are present in patients with systemic lupus erythematosus and antiphospholipid syndrome and are associated with the pathogenesis of the disease. Anti-endothelial cell antibodies that react with constitutive antigens on ECs are present in patients with vasculiditis and other diseases. Both types of antibodies can activate ECs. Frequent findings in APLS and vasculitis are fibrin deposits and thromboembolic phenomena. These indicate that the coagulation system is activated. However, the mechanism of activation is not clear. ECs generate tissue factor upon stimulation with various substances. In the present study we report that monoclonal anti-beta 2-GPI antibodies and AECAs, derived from a patient with primary APLS and a patient with Takayasu's arteritis, respectively, induce a potent tissue factor in ECs. The production of TF activity, TF antigen and TF mRNA is dose and time dependent. The TF activity was induced also by F(ab)2 but not by Fc fragments and was abolished completely by pre-incubation with ant-TF antibodies. The TF that is induced in ECs by AECAs with and without beta 2-GPI specificity may activate the coagulation and thereby play a major role in the pathogenesis of fibrin deposition and thrombus formation in diseases that are associated with the presence of these antibodies.
Kornberg
A
A
Institute of Hematology, Assaf Harofeh Medical Center, Zerifin, Israel.
Renaudineau
Y
Y
Blank
M
M
Youinou
P
P
Shoenfeld
Y
Y
D000906:Antibodies / Q000276:immunology*; D000941:Antigens / Q000276:immunology; D016736:Antiphospholipid Syndrome / Q000276:immunology; D001053:Apolipoproteins / Q000276:immunology*; D001666:Binding Sites, Antibody / Q000276:immunology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology*; D005337:Fibrin / Q000276:immunology / Q000378:metabolism; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007141:Immunoglobulin Fc Fragments / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D013625:Takayasu Arteritis / Q000276:immunology; D013923:Thromboembolism / Q000209:etiology / Q000276:immunology; D013925:Thromboplastin / Q000235:genetics / Q000276:immunology*; D014657:Vasculitis / Q000276:immunology; D053482:beta 2-Glycoprotein I
D000906:Antibodies; D000941:Antigens; D001053:Apolipoproteins; D006023:Glycoproteins; D007140:Immunoglobulin Fab Fragments; D007141:Immunoglobulin Fc Fragments; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D053482:beta 2-Glycoprotein I; D005337:Fibrin; D013925:Thromboplastin