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Published on: March 25, 2016
Anticardiolipin, but not the 16/6 Id anti-DNA antibody induces pregnancy failure
Z M Sthoeger1, B Tartakovsky, M Fogel
1Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
Insights
Anticardiolipin antibodies, but not anti-DNA antibodies, cause pregnancy failure in mice. This research clarifies the role of specific antibodies in antiphospholipid syndrome and gestational impairment.
Area of Science:
- Immunology
- Reproductive Medicine
- Autoimmunity
Background:
- Antiphospholipid syndrome (APS) involves thrombosis, thrombocytopenia, and fetal loss, linked to anticardiolipin antibodies.
- The causal role of these antibodies in pregnancy failure requires further investigation.
Purpose of the Study:
- To determine if anticardiolipin antibodies cause pregnancy failure.
- To investigate the effects of anti-DNA and anticardiolipin monoclonal antibodies on pregnancy outcomes in a mouse model.
Main Methods:
- BALB/c mice were immunized with either a 16/6 Id anti-DNA monoclonal antibody or a 2C4C2 anticardiolipin monoclonal antibody.
- Pregnancy outcomes, including pregnancy rate, fetal numbers, and resorption rates, were assessed.
- Anticardiolipin antibody levels in sera were correlated with pregnancy fate.
Main Results:
- Immunization with the 16/6 Id anti-DNA antibody resulted in normal pregnancy outcomes.
- Immunization with the 2C4C2 anticardiolipin antibody led to severe gestational failure, characterized by low pregnancy rates, reduced fetal numbers, and high resorption rates.
- A direct correlation was observed between high anticardiolipin antibody levels and severe pregnancy impairment.
Conclusions:
- Anticardiolipin antibodies, specifically demonstrated by the 2C4C2 antibody, can induce severe gestational impairment.
- Anti-DNA antibodies (16/6 Id) did not cause pregnancy failure in this model.
- These findings highlight the pathogenic role of anticardiolipin antibodies in pregnancy loss associated with antiphospholipid syndrome.
Abstract:
The primary antiphospholipid syndrome or the antiphospholipid syndrome in systemic lupus erythematosus patients (defined as secondary antiphospholipid syndrome) are characterized by the presence of thrombosis, thrombocytopenia and recurrent fetal loss in association with anticardiolipin antibodies. To determine the causal role of these antibodies in the pathogenesis of pregnancy failure we studied the effects of immunization with monoclonal anti-DNA antibody (designated 16/6 Id; no cardiolipin reactivity) and anticardiolipin monoclonal antibody (designated 2C4C2; binds DNA as well) on the outcome of allogeneic pregnancies in BALB/c mice. Mating of BALB/c females 4 weeks after active immunization with the 16/6 Id, anti-DNA monoclonal antibody resulted in normal pregnancy outcome, similar to control mouse groups. In contrast to that, immunization with the 2C4C2 anticardiolipin antibodies resulted in severe gestational failure with low pregnancy rate, low numbers of fetuses 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 control groups. Furthermore, a correlation was shown between the presence of anticardiolipin antibody levels in the sera of the mice at the time of gestation and the pregnancy fate. The 2C4C2-immunized mice which produced high levels of anticardiolipin antibodies demonstrated severe pregnancy failure, whereas normal gestations were observed in the 16/6 Id primed or the control mouse groups that did not produce measurable amounts of the latter antibodies. Thus, our studies demonstrate that anticardiolipin but not the 16/6 Id anti-DNA antibodies can induce severe gestational impairment.
