Endothelial cells as target for antiphospholipid antibodies. Human Polyclonal and Monoclonal Anti‐β 2 ‐Glycoprotein I Antibodies React In Vitro with Endothelial Cells Through Adherent β 2 ‐Glycoprotein I and Induce Endothelial Activation

Objective. To investigate the ability of human anti‐β 2 ‐glycoprotein I (anti‐β 2 GPI) antibodies to recognize the cofactor adherent on endothelial cells (EC) and to modulate endothelial functions. Methods. Six human affinity‐purified polyclonal anti‐β 2 GPI IgG and 2 IgM monoclonal antibodies (MAb) were obtained from patients with the antiphos‐pholipid syndrome. The antibodies were tested for their ability to 1) bind to endothelial monolayers through the adherent β 2 GPI and 2) modulate endothelial adhesion molecule expression and interleukin‐6 (IL‐6) and 6‐keto‐prostaglandin F 1α (6‐keto‐PGF 1α ) secretion. Results. The affinity‐purified IgG and the MAb with anti‐β 2 GPI activity, but not the respective controls, displayed EC binding, which declined on cells incubated in serum‐free medium and was restored in a dose‐dependent manner by exogenous human β 2 GPI. After EC binding, both polyclonal and monoclonal antibodies up‐regulated adhesion molecule expression. Anti‐β 2 GPI MAb also significantly increased IL‐6 and 6‐keto‐PGF 1α secretion. Conclusion. These findings support the hypothesis that anti‐β 2 GPI antibodies bind and activate EC through the adherent cofactor β 2 GPI, likely leading to a procoagulant state.