THROMBOGENIC PROPERTIES OF MURINE ANTICARDIOLIPIN ANTIBODIES INDUCED BY BETA(2) GLYCOPROTEIN-1 AND HUMAN-IMMUNOGLOBULIN-G ANTIPHOSPHOLIPID ANTIBODIES

Background Recurrent arterial thrombosis and venous thrombosis are fre quent complications of the antiphospholipid syndrome (APS). Patients p roduce anti-cardiolipin antibodies, but the role of these antibodies i n thrombus formation is uncer tain. This study used a unique CD-1 mous e model of thrombosis to determine whether anti-cardiolipin and anti-b eta(2) glycoprotein 1 (beta 2GP1) antibodies induced immunologically i n these animals are thrombogenic. Methods and Results The CD-1 mouse m odel enables measurement of the kinetics of a thrombus induced in the femoral vein of the animal. Animals are first anesthetized, then one f emoral vein is exposed and subjected to a standardized, nonpenetrating ''pinch'' injury that induces a thrombus. The vein is trans-illuminat ed, and the growing thrombus is visualized on a television screen. The rate of formation and disappearance of the thrombus as well as its ar ea can be measured by a computer attached to the television. Three gro ups of CD-1 mice (each group comprising seven animals) were studied. G roup 1 mice were actively immunized with beta(2)GP1, resulting in prod uction of anti-beta(2)GP1 and anti-cardiolipin antibodies. Group 2 mic e were actively immunized with human immunoglobulin G (IgG) anticardio lipin antibodies and produced anti-human IgG as well as anti-cardiolip in antibodies (the latter by an idiotype-anti-idiotype reaction). Thes e animals did net produce anti-beta(2)GP1 antibodies. Group 3 mice wer e immunized with human serum albumin (HSA) and produced anti-HSA but n ot anti-cardiolipin antibodies. The kinetics of thrombus formation ind uced in the femoral veins of the experimental mice were compared. Resu lts showed that the mean thrombus area as well as mean time during whi ch thrombi persisted were significantly greater in group 1 and group 2 mice compared with group 3. There was no statistical difference betwe en group I or group 2. Conclusions Demonstration of a thrombogenic eff ect of murine anti-cardiolipin antibodies suggests that these antibodi es may be pathogenic in humans with APS.