Mice and Mothers: Understanding Pregnancy Complications in Patients with Autoimmunity

Systemic lupus erythematosus (SLE) is an autoimmune disease that predominantly affects women and presents during their childbearing years. Pregnancy in these women is dangerous both for mother and offspring, and, in the past, patients were advised not to have children. Among complications frequently seen in women with lupus is preeclampsia (also known as toxemia of pregnancy), preterm birth, markedly underweight newborns, and fetal death. Identifying women destined for complications remains challenging and limits our ability to counsel and care for pregnant lupus patients.

There is currently no effective treatment for women with these high-risk pregnancies; treatments to prevent poor pregnancy outcomes require an understanding of mechanisms of injury. Our research in an animal model that mimics the human condition shows that the blockade of well-established mediators of inflammation prevents adverse outcomes. To translate these discoveries to lupus patients, we launched the PROMISSE Study (Predictors of Pregnancy Outcome: bioMarkers In antiphospholipid antibody Syndrome and Systemic lupus Erythematosus) to determine which pregnancies were at highest risk for adverse outcomes. Over 20% of pregnancies in patients with SLE resulted in an adverse pregnancy outcome. We discovered a specific auto-antibody that can be detected in the blood before pregnancy or in the first trimester, confers a 10-fold increase in risk of complications. Furthermore, we found that early in pregnancy, measurable alterations in the balance of angiogenic factors (proteins that circulate in blood, promote proper placenta development, and are required to maintain the health of the mother’s vascular system) are highly predictive of preeclampsia and other pregnancy complications.

The results of the PROMISSE Study provide models for early risk stratification to allow physicians to identify patients early in pregnancy who are at low risk and reassure them that their pregnancies were likely to be uncomplicated and their babies healthy. Conversely and importantly, we can reliably predict which patients are destined to have poor pregnancy outcomes, and we are working to offer patients at the highest risk an experimental therapy to prevent placental dysfunction. Treatments to prevent poor pregnancy outcomes require an understanding of mechanisms of injury. Experiments in mouse models have enabled us to embark upon a trial of a potential treatment.