Endothelial cells as target for antiphospholipid antibodies. Human Polyclonal and Monoclonal Anti‐β2‐Glycoprotein I Antibodies React In Vitro with Endothelial Cells Through Adherent β2‐Glycoprotein I and Induce Endothelial Activation

Abstract

Objective. To investigate the ability of human anti‐β₂‐glycoprotein I (anti‐β₂GPI) antibodies to recognize the cofactor adherent on endothelial cells (EC) and to modulate endothelial functions. Methods. Six human affinity‐purified polyclonal anti‐β₂GPI 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 β₂GPI 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‐β₂GPI 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 β₂GPI. After EC binding, both polyclonal and monoclonal antibodies up‐regulated adhesion molecule expression. Anti‐β₂GPI MAb also significantly increased IL‐6 and 6‐keto‐PGF_1α secretion. Conclusion. These findings support the hypothesis that anti‐β₂GPI antibodies bind and activate EC through the adherent cofactor β₂GPI, likely leading to a procoagulant state.