Regulatory effect of antiphospholipid antibodies on signal transduction: a possible model for autoantibody-induced reproductive failure.

Abstract

The broad range of reproductive processes apparently affected by antiphospholipid antibodies suggests that antiphospholipid antibodies have to exert their clinical effects at every basic cellular level. Because phospholipids constitute essential components of every cell membrane, and because signal transduction processes are dependent on second messengers with phospholipid epitopes, we investigated the hypothesis that interference with signal transduction processes by antiphospholipid antibodies could represent such a basic cellular process. To test this hypothesis we established an in vitro placental culture system in which the stimulation of explants by phospholipase A2 and phospholipase C in the presence of normal human serum resulted in a significant increase in human chorionic gonadotropin secretion. When normal human sera were replaced with antiphospholipid antibody-containing sera from two women with established histories of reproductive failure, this increase in human chorionic gonadotropin production was inhibited 42% to 44% under phospholipase A2 stimulation and by 34% to 39% under phospholipase C stimulation. The hypothesis that antiphospholipid antibodies can interfere with signal transduction processes was further strengthened by the observation that antiphospholipid antibody-positive sera contained significantly higher immunoglobulin A antibody reactivity toward the second messenger inositol 1,4,5-triphosphate than control sera (p less than 0.049). These observations suggest the possibility that if present at excessive levels antiphospholipid antibodies may exert their adverse effect on reproductive processes through the interception of signal transduction processes.