Induction of antiphospholipid antibodies by peptide immunization and proof of their pathogenicity in an animal model

Excerpt

Antiphospholipid (aPL) antibodies (Abs) represent autoantibodies associated with thrombosis, pregnancy loss, and thrombocytopenia in patients with SLE or primary aPL syndrome. The induction of these autoantibodies remains enigmatic. Phospholipid (PL) alone is not able to induce autoantibodies, whereas a variety of studies could demonstrate that cardiolipin complexed with Staphylococcus aureus, Salmonella minnesota particles have the capacity to induce aPL. However, generation of these antibodies did not result in pathogenic effects when studied in applied experimental settings. Notably, ?2glycoprotein I (?2GPI), also known as apolipoprotein H, is a cofactor for binding of aPL to cardiolipin. It has been previously shown that aPL can be generated in mice by immunization with ?2GPI and these Abs were thrombogenic and caused pregnancy loss in mice. To test whether aPL induced by immunization with a 15 amino acid polypeptide, including the phospholipid-binding site of ?2GPI is thrombogenic and activates endothelial cells (EC) in vivo and in vitro. …