A model for the antiphospholipid antibody syndrome: monoclonal antiphosphatidylserine antibody induces intrauterine growth restriction in mice.

Abstract

Antiphospholipid antibodies are associated with clinical intrauterine growth restriction. In this study we investigated whether immunoglobulin M monoclonal antibodies against phosphatidylserine or cardiolipin or cross-reactive with both phospholipids would induce intrauterine growth restriction in an experimental model of the antiphospholipid antibody syndrome. Balb/c or CD-1 mice were injected intraperitoneally on day 8 of pregnancy with three immunoglobulin M monoclonal antibodies that differentiated between cardiolipin- and phosphatidylserine-dependent antigens or with control immunoglobulin M monoclonal antibodies against irrelevant antigens. The animals were killed on day 15 of pregnancy and placental and fetal weights were measured. Monoclonal antibody 3SB9b, which reacted in enzyme-linked immunosorbent assays with phosphatidylserine but not cardiolipin, induced a significant reduction in both fetal and placental weights. Monoclonal antibodies BA3B5C4, which was cross-reactive with cardiolipin and phosphatidylserine, and D11A4, which reacted with cardiolipin, did not alter fetoplacental weights. An antiphospholipid antibody that reacts with phosphatidylserine induces significant fetal and placental intrauterine growth restriction in a mouse model for the antiphospholipid antibody syndrome, but those that react with cardiolipin do not.