ANTICARDIOLIPIN, BUT NOT THE 16 6 ID ANTI-DNA ANTIBODY INDUCES PREGNANCY FAILURE/

The primary antiphospholipid syndrome or the antiphospholipid syndrome in systemic lupus erythematosus patients (defined as secondary antiph ospholipid syndrome) are characterized by the presence of thrombosis, thrombocytopenia and recurrent fetal loss in association with anticard iolipin antibodies. To determine the causal role of these antibodies i n the pathogenesis of pregnancy failure we studied the effects of immu nization with monoclonal anti-DNA antibody (designated 16/6 Id; no car diolipin reactivity) and anticardiolipin monoclonal antibody (designat ed 2C4C2; binds DNA as well) on the outcome of allogeneic pregnancies in BALB/c mice. Mating of BALB/c females 4 weeks after active immuniza tion with the 16/6 Id, anti-DNA monoclonal antibody resulted in normal pregnancy outcome, similar to control mouse groups. In contrast to th at, immunization with the 2C4C2 anticardiolipin antibodies resulted in severe gestational failure with low pregnancy rate, low numbers of fe tuses and high rates of resorptions. The fertility index of those mice was extremely low as compared to the 16/6 Id-immunized mice or the co ntrol groups. Furthermore, a correlation was shown between the presenc e of anticardiolipin antibody levels in the sera of the mice at the ti me of gestation and the pregnancy fate. The 2C4C2-immunized mice which produced high levels of anticardiolipin antibodies demonstrated sever e pregnancy failure, whereas normal gestations were observed in the 16 /6 Id primed or the control mouse groups that did not produce measurab le amounts of the latter antibodies. Thus, our studies demonstrate tha t anticardiolipin but not the 16/6 Id anti-DNA antibodies can induce s evere gestational impairment.