Induction of phospholipid-binding antibodies in mice and rabbits by immunization with human β2 glycoprotein 1 or anticardiolipin antibodies alone

Authors

  • S. S. PIERANGELI,

    Corresponding author
    1. Antiphospholipid Standardization Laboratory, Department of Medicine, University of Louisville, Louisville, KY, USA
      Silvia S. Pierangeli PhD, Division of Rheumatology, Department of Medicine, University of Louisville, Louisville, KY 40292, USA.
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  • E. N. HARRIS

    1. Antiphospholipid Standardization Laboratory, Department of Medicine, University of Louisville, Louisville, KY, USA
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Silvia S. Pierangeli PhD, Division of Rheumatology, Department of Medicine, University of Louisville, Louisville, KY 40292, USA.

SUMMARY

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 β2glycoprotein 1 (β2GPI)in Freund's complete adjuvant (FCA) resulted in aCL antibody production in the recipient mice. Since this observation might explain how autoantibodics 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 β2GP1 mixed with adjuvants that did not contain lipids (Adju-Prime or aluminium hydroxide). This excluded the possibility that antibody induction occurred because β2GPl formed complexes with lipids in FCA. We also found that aCL antibodies always appeared before anti-β2GPl antibodies, excluding the possibility that aCL antibodies were directed to β2GP1 or were induced by formation of anti-idiotypic antibodies (to anti-β2GPl). 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 arc 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.

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