Lupus anticoagulant (LAC) is an autoantibody that is associated with recurrent first-trimester abortion and second-trimester fetal death, with 80% or more of pregnancies in women with the anticoagulant ending in fetal wastage. In pregnancies that progress beyond mid-gestation, severe or early preeclampsia and fetal growth retardation are common. LAC is commonly detected by its prolongation-effect on phospholipid-dependent coagulation, and the antibody has been identified as an anti-phospholipid. The pathophysiologic effect of LAC has been attributed to the inhibition of vascular prostacyclin production that has been observed in vitro in the presence of the antibody. We propose to study two aspects of LAC. First, we will evaluate the specific antigen-antibody interactions for LAC using an immunologic assay that we have developed. Our preliminary results suggest that the antigen is the phospholipid, phosphatidylserine. Secondly, we will study the mechanism of LAC using a prostacyclin generation assay and mouse and rabbit models of reproduction. The animals will be actively immunized with various phospholipid preparations or passively immunized with purified human LAC preparations or human or mouse monoclonal LAC, and their reproductive performance evaluated.
