Beta₂‐glycoprotein I in thrombosis: evidence for a role as a natural anticoagulant

Abstract

Although the physiological role of beta2-glycoprotein (B2GPI) is unknown, in vitro evidence indicates that B2GPI may be a natural anticoagulant. In this study we have examined whether fluctuations of plasma B2GPI occur in in vivo coagulation. Serial measurements of B2GPI and other anticoagulant proteins were performed in 51 patients with thrombotic (group 1: six patients with disseminated intravascular coagulation (DIC), group 2: venous (n = 4) or arterial (n = 170 thrombosis) and non-thrombotic disease (group 3: 24 patients undergoing elective surgery). Reductions in plasma B2GPI levels were seen in most patients which were roughly proportional to the severity of their illness. Particularly striking reductions of B2GPI, protein C (PC) and antithrombin III (AT-III) (mean +/- 95% CI: 42.7 +/- 8.6%, 42.1 +/- 14.8%, 39.1 +/- 28.4% respectively) were seen in group 1. The reductions in plasma B2GPI were significantly greater in group 1 than in the other groups. Dilutional factors explain most of the reductions in B2GPI, PC and AT-III in groups 2 and 3, but contribute little to group 1. In conclusion, although B2GPI behaves as a 'negative acute phase reactant', the magnitude of reduction of plasma B2GPI levels, accompanied by reductions in other anticoagulant proteins in patients with DIC, suggests specific consumption of B2GPI in in vivo coagulation. This study provides further evidence that B2GPI is an anticoagulant of physiological importance.

Immune Clearance of Phosphatidylserine-expressing Cells by Phagocytes

“…Although the in vivo function of ␤ 2 GPI has not been investigated in detail, it is known to strongly interact with plasma proteins (20) and play a role in regulating coagulation (12) and immune clearance (13). Recent studies have shown that intravenously injected liposomes containing negatively charged phospholipids rapidly bind ␤ 2 GPI, a result that directly correlated with the clearance rates of the vesicles.…”

“…Recent studies have raised the possibility that autologous serum proteins might bind PS-expressing cells. Indeed, evidence has been presented suggesting that at least one of these proteins, ␤ 2 -glycoprotein I (␤ 2 GPI), could play a critical role in regulating platelet-dependent thrombosis (12) and clearance of liposomes containing negatively charged lipids (13).…”

The effect of platelet activation on the hypercoagulability induced by murine monoclonal antiphospholipid antibodies

“…As shown in Figure 2C, prothrombin alone had no effect whereas platelet procoagulant activity values were statistically reduced upon addition of β2GPI (p=0.01), in line with the reported anticoagulant effect of this latter protein. 21 Platelet procoagulant activity values obtained with murine IgG, 28F4 or 7F6G were not different from those of the control (unstimulated washed platelets). In the presence of their target, murine monoclonal antibodies induced a significant increase in platelet procoagulant activity compared with the antibody alone.…”

Immunocamouflage of latex surfaces by grafted methoxypoly(ethylene glycol) (mPEG): Proteomic analysis of plasma protein adsorption

“…The binding of beta-2-glycoprotein I precursor and thrombospondin could potentially serve beneficial functions in cell and tissue transplantation. Beta-2-glycoprotein binds to negatively charged phospholipids and inhibits the coagulation cascade [30,31], while thrombospondin-1 is a potent inhibitor of T-cell and dendritic cell activation [32,33].…”