β2-glycoprotein I-dependent anticardiolipin antibodies preferentially bind the amino terminal domain of β2-glycoprotein I

Many of the autoantibodies in antiphospholipid syndrome (APS) are directed against beta (2)-glycoprotein I (beta (2)-GPI). Recent studies from our laboratories have indicated that the immunodominant binding epitope(s) for high titer, affinity purified antibodies from I I APS patients are localized to the amino terminal domain (domain 1) of beta (2)- GPI. The present study employed surface plasmon resonance to localize the immunodominant domain in serum samples from a large cohort of patients with GPL values ranging from 21 to 230 units (n = 106 patients). Eighty-eight percent of patients showed greater than or equal to threefold selectivity for beta (2)-GPI containing domain I relative to the domain deletion mutant that lacked domain 1. The domain I binding activity in patient serum was abolished by removing the I-G fraction from the serum and the binding activity could be fully reconstituted with the IgG fraction. Thus, analysis of serum samples from a large cohort of APS patients indicates that the immunodominant binding epitope(s) for anti-beta (2) antibodies are localized to the amino terminal domain of beta (2)-GPI.