title: In vitro studies of antiphospholipid antibodies and its cofactor, beta 2-glycoprotein I, show negligible effects on endothelial cell mediated protein C activation.
abstract: The effect of sera and purified IgG isolated from plasma of 46 patients with systemic lupus erythematosus (SLE) and 9 healthy donors on the endothelial cell (EC) mediated protein C activation was investigated. Out of the 46 SLE sera used, 19 were antiphospholipid antibodies (aPL) positive. From 12 patients IgG was isolated, of which 6 contained aPL. EC were first incubated with IgG (7 mg/ml) or serum (1:1 diluted) for 1 h and then tested for their ability to promote protein C activation by thrombin, with the cells either in a monolayer or in a suspension. The normal range (mean of control values +/- 2 SD) of protein C activation was 80-120%. In contrast to others, we could not detect an inhibition of protein C activation by any of the patient IgG's or sera. The recently described cofactor for binding of antiphospholipid antibodies to phospholipids, beta 2-glycoprotein I, was purified and added to the purified IgG's. A combination of these two components did not inhibit the EC mediated protein C activation by thrombin. This study suggests that the inhibition of the protein C activation, mediated by EC, is not a general mechanism by which aPL related thrombosis can be explained.
authors.affiliation: Department of Haematology, University Hospital Utrecht, The Netherlands.
authors.forename: J D
authors.initials: JD
authors.lastname: Oosting
authors.forename: R H
authors.initials: RH
authors.lastname: Derksen
authors.forename: T M
authors.initials: TM
authors.lastname: Hackeng
authors.forename: M
authors.initials: M
authors.lastname: van Vliet
authors.forename: K T
authors.initials: KT
authors.lastname: Preissner
authors.forename: B N
authors.initials: BN
authors.lastname: Bouma
authors.forename: P G
authors.initials: PG
authors.lastname: de Groot
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000276:immunology*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology*; D005260:Female; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000302:isolation & purification; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010743:Phospholipids / Q000276:immunology*; D011486:Protein C / Q000276:immunology* / Q000302:isolation & purification; D053482:beta 2-Glycoprotein I
chemical_list: D000911:Antibodies, Monoclonal; D006023:Glycoproteins; D007074:Immunoglobulin G; D010743:Phospholipids; D011486:Protein C; D053482:beta 2-Glycoprotein I