Effect of beta 2glycoprotein I and human monoclonal anticardiolipin antibody on the protein S/C4b-binding protein system.
The effect of beta 2glycoprotein I (beta 2GPI) and human monoclonal anticardiolipin antibody (aCL) on the protein S/C4b-binding protein (C4BP) system was evaluated. The binding of C4BP to protein S was assessed by ELISA in the presence of beta 2GPI with/without human monoclonal aCL. beta 2GPI downregulated the binding between S and C4BP significantly. Human monoclonal aCL abolished the beta 2GPI inhibitory effect in a calcium (Ca++) independent fashion. In separate experiments, the reactivity of aCL towards protein S in the presence or absence of beta 2GPI and cardiolipin was investigated. Monoclonal aCL bound to protein S only in the presence of a combination of beta 2GPI and cardiolipin. This binding was Ca++ dependent. These findings suggest that human monoclonal aCL increases the affinity of C4BP for protein S, and that protein S may represent one of the targets for aCL when combined with beta 2GPI and cardiolipin. Both issues may explain acquired free protein S deficiency and the attendant risk of thrombosis in patients with aCL.
Atsumi
T
T
Lupus Research Unit, Rayne Institute, St. Thomas' Hospital, London, UK.
Khamashta
M A
MA
Ames
P R
PR
Ichikawa
K
K
Koike
T
T
Hughes
G R
GR
D000818:Animals; D017153:Antibodies, Anticardiolipin / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001053:Apolipoproteins / Q000494:pharmacology; D001402:B-Lymphocytes / Q000276:immunology; D015935:Complement C4b / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D006023:Glycoproteins / Q000494:pharmacology*; D006801:Humans; D006825:Hybridomas; D007075:Immunoglobulin M; D007700:Kinetics; D051379:Mice; D018448:Models, Immunological; D008961:Models, Structural; D011485:Protein Binding; D017293:Protein S / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D053482:beta 2-Glycoprotein I
D017153:Antibodies, Anticardiolipin; D000911:Antibodies, Monoclonal; D001053:Apolipoproteins; D006023:Glycoproteins; D007075:Immunoglobulin M; D017293:Protein S; D053482:beta 2-Glycoprotein I; D015935:Complement C4b