Thrombogenic Properties of Murine Anti-Cardiolipin Antibodies Induced by β 2 Glycoprotein 1 and Human Immunoglobulin G Antiphospholipid Antibodies

Abstract

Background Recurrent arterial thrombosis and venous thrombosis are frequent complications of the antiphospholipid syndrome (APS). Patients produce anti-cardiolipin antibodies, but the role of these antibodies in thrombus formation is uncertain. This study used a unique CD-1 mouse model of thrombosis to determine whether anti-cardiolipin and anti-β 2 glycoprotein 1 (β 2 GP1) antibodies induced immunologically in these animals are thrombogenic. Methods and Results The CD-1 mouse model enables measurement of the kinetics of a thrombus induced in the femoral vein of the animal. Animals are first anesthetized, then one femoral vein is exposed and subjected to a standardized, nonpenetrating “pinch” injury that induces a thrombus. The vein is transilluminated, and the growing thrombus is visualized on a television screen. The rate of formation and disappearance of the thrombus as well as its area can be measured by a computer attached to the television. Three groups of CD-1 mice (each group comprising seven animals) were studied. Group 1 mice were actively immunized with β 2 GP1, resulting in production of anti-β 2 GP1 and anti-cardiolipin antibodies. Group 2 mice were actively immunized with human immunoglobulin G (IgG) anti-cardiolipin antibodies and produced anti-human IgG as well as anti-cardiolipin antibodies (the latter by an idiotype–anti-idiotype reaction). These animals did not produce anti-β 2 GP1 antibodies. Group 3 mice were immunized with human serum albumin (HSA) and produced anti-HSA but not anti-cardiolipin antibodies. The kinetics of thrombus formation induced in the femoral veins of the experimental mice were compared. Results showed that the mean thrombus area as well as mean time during which thrombi persisted were significantly greater in group 1 and group 2 mice compared with group 3. There was no statistical difference between group 1 or group 2. Conclusions Demonstration of a thrombogenic effect of murine anti-cardiolipin antibodies suggests that these antibodies may be pathogenic in humans with APS.