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.