INDUCTION OF PHOSPHOLIPID-BINDING ANTIBODIES IN MICE AND RABBITS BY IMMUNIZATION WITH HUMAN BETA-2 GLYCOPROTEIN-1 OR ANTICARDIOLIPIN ANTIBODIES ALONE

Anticardiolipin (aCL) antibodies are autoantibodies present in high co ncentrations in patients with the antiphospholipid syndrome (APS), a d isorder of recurrent thrombosis and pregnancy loss. What induces aCL a ntibodies is uncertain, but a recent report suggested that immunizatio n of mice with beta2glycoprotein 1 (beta2GP1) in Freund's complete adj uvant (FCA) resulted in aCL antibody production in the recipient mice. Since this observation might explain how autoantibodies might be indu ced by poor immunogens, such as phospholipids, we decided to explore t he question further. In our first series of experiments, we found that aCL antibodies were induced in mice by beta2GP1 mixed with adjuvants that did not contain lipids (Adju-Prime or aluminium hydroxide). This excluded the possibility that antibody induction occurred because beta 2GP1 formed complexes with lipids in FCA. We also found that aCL antib odies always appeared before anti-beta2GP1 antibodies, excluding the p ossibility that aCL antibodies were directed to beta2GP1 or were induc ed by formation of anti-idiotypic antibodies (to anti-beta2GP1). In ex periments, we found that immunization of mice with human IgG antibodie s from patients with the APS (IgG-APS), also induced aCL antibodies. I mmunization with pure bovine serum albumin (BSA) did not induce aCL an tibodies. We propose that aCL antibodies are induced by proteins with high avidity for phospholipids. These proteins may be bound to phospho lipids when introduced, or may bind circulating phospholipids, so tran sforming phospholipid molecules into immunogens. Similar mechanisms mi ght explain autoantibody induction to other poor immunogens.