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 antiphospholipid 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.
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