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 concentrations in patients with the antiphospholipid syndrome (APS), a disorder of recurrent thrombosis and pregnancy loss. What induces aCL antibodies is uncertain, but a recent report suggested that immunization of mice with beta 2 glycoprotein 1 (beta 2 GP1) in Freund's complete adjuvant (FCA) resulted in aCL antibody production in the recipient mice. Since this observation might explain how autoantibodies might be induced by poor immunogens, such as phospholipids, we decided to explore the question further. In our first series of experiments, we found that aCL antibodies were induced in mice by beta 2GP1 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 antibodies always appeared before anti-beta 2GP1 antibodies, excluding the possibility that aCL antibodies were directed to beta 2GP1 or were induced by formation of anti-idiotypic antibodies (to anti-beta 2GP1). In experiments, we found that immunization of mice with human IgG antibodies from patients with the APS (IgG-APS), also induced aCL antibodies. Immunization with pure bovine serum albumin (BSA) did not induce aCL antibodies. We propose that aCL antibodies are induced by proteins with high avidity for phospholipids. These proteins may be bound to phospholipids when introduced, or may bind circulating phospholipids, so transforming phospholipid molecules into immunogens. Similar mechanisms might explain autoantibody induction to other poor immunogens.
Pierangeli
S S
SS
Department of Medicine, University of Louisville, KY 40292.
Harris
E N
EN
D000818:Animals; D017153:Antibodies, Anticardiolipin / Q000276:immunology*; D017152:Antibodies, Antiphospholipid / Q000096:biosynthesis*; D001053:Apolipoproteins / Q000276:immunology*; D002417:Cattle; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D011817:Rabbits; D053482:beta 2-Glycoprotein I
D017153:Antibodies, Anticardiolipin; D017152:Antibodies, Antiphospholipid; D001053:Apolipoproteins; D006023:Glycoproteins; D053482:beta 2-Glycoprotein I