Anti-DNA antibodies cross-reacting with laminin inhibit trophoblast attachment and migration: Implications for recurrent pregnancy loss in SLE patients

PROBLEM: Systemic lupus erythematosus (SLE), an autoimmune disease, is asso ciated with reduced fetal survival, recurrent abortions, and other pregnanc y complications. Some of the autoantibodies found in SLE bind to laminins ( LNs), which play an important role in the implantation of the fertilized ov um in humans. METHOD OF STUDY: To elucidate the role of these specific autoantibodies, ch orionic villous explants from 6-7-week-old human placentas were established as organ cultures on laminin-1 (LN-1), collagen IV (CN-IV) or uncoated cul ture dishes. The cultures were then exposed to a mouse monoclonal anti-DNA/ anti-LN-1 antibody, to human polyclonal lupus antibodies cross-reacting wit h LN-1, a function-blocking polyclonal antibody to LN-1, polyclonal antibod ies to CN-IV, or IgG control. RESULTS: The explants attached to LN-1 and CN-IV, but not to uncoated cultu re dishes. LN-1 promoted migration of trophoblast, whereas CN-IV promoted m igration of fibroblast-like cells. Trophoblast attachment and migration wer e abolished in a dose-dependent manner by all three antibodies to LN-1, but not by antibodies to CN-IV or IgG control. Furthermore, the effect of anti -LN antibodies was abolished by preincubating them with LN-1. CONCLUSIONS: These studies suggest that anti-DNA antibodies cross-reacting with LNs may play a role in early pregnancy failure in SLE patients by inte rfering with placental implantation.