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 (6-keto-PGF) 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 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.