Antiphospholipid antibodies: new perspectives on antigenic specificity

Antiphospholipid antibodies (aPL) are found in up to 60% of patients with systemic lupus erythematosus (SLE), and appear to predispose to a number of complications of the disease. We purified IgG from patients with SLE and the antiphospholipid antibody syndrome (APS) who have high levels of aPL and used this IgG in a modified ELISA where we excluded any source of cofactor in the assay. We showed that for 10 of the 11 patients, IgG bound strongly to cardiolipin only in the presence of the cofactor, which was present in fetal calf serum, normal human serum (NHS), and in the infranatant lipoprotein fractions obtained by flotation ultracentrifugation of NHS. We then purified beta 2 glycoprotein I (beta 2GPI) from NHS and showed that for 9 of the 11 samples of IgG, beta 2GPI was as effective, or more effective, than NHS as a source of cofactor. When beta 2GPI was coated on ELISA plate and used as an antigen we found little or no reactivity of patient sera or IgG, suggesting that beta 2GPI alone is not antigenic in our system. Three possible explanations could be put forward to explain the behavior of cardiolipin and beta 2GPI, neither of which is antigenic alone.