UCL logo

UCL Discovery

UCL home » Library Services » Electronic resources » UCL Discovery

Thrombin Binding Predicts the Effects of Sequence Changes in a Human Monoclonal Antiphospholipid Antibody on Its In Vivo Biologic Actions

Giles, I; Perieleous, C; Liu, XW; Ehsanullah, J; Clarke, L; Brogan, P; Newton-West, M; ... Rahman, A; + view all (2009) Thrombin Binding Predicts the Effects of Sequence Changes in a Human Monoclonal Antiphospholipid Antibody on Its In Vivo Biologic Actions. J IMMUNOL , 182 (8) 4836 - 4843. 10.4049/jimmunol.0804241.

Full text not available from this repository.

Abstract

The mechanisms by which anti phospholipid Abs (aPL) cause thrombosis are not fully understood. It is clear that binding to a number of phospholipid-associated Ags is important but it is difficult to identify which Ag-binding properties are most closely linked to the ability to cause biologic effects such as promotion of thrombosis and activation of endothelial cells. We have previously used an in vitro expression system to produce a panel of human monoclonal IgG molecules between which we engineered small differences in sequence leading to significant well-defined changes in binding properties. In this study, we assess the properties of five of these IgG molecules in assays of biologic function in vitro and in vivo. The i.p.injection of these IgG into mice subjected to a femoral vein pinch stimulus showed that only those IgG that showed strong binding to thrombin promoted in vivo venous thrombosis and leukocyte adherence. However, this finding did not hold true for the effects of these IgG on activation of cultured endothelial cells in vitro, where there was a less clear relationship between binding properties and biologic effects. The Journal of Immunology, 2009, 182: 4836-4843.

Type: Article
Title: Thrombin Binding Predicts the Effects of Sequence Changes in a Human Monoclonal Antiphospholipid Antibody on Its In Vivo Biologic Actions
DOI: 10.4049/jimmunol.0804241
Keywords: SYSTEMIC-LUPUS-ERYTHEMATOSUS, ENDOTHELIAL-CELL ACTIVATION, TISSUE FACTOR EXPRESSION, ARGININE RESIDUES, UP-REGULATION, MICROPARTICLES, CARDIOLIPIN, ANTIGEN, ANTI-BETA(2)-GLYCOPROTEIN-I, IMMUNOGLOBULIN
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > UCL GOS Institute of Child Health > ICH - Directors Office
URI: http://discovery.ucl.ac.uk/id/eprint/172052
Downloads since deposit
0Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item