Failing maternal-fetal tolerance in Systemic Lupus Erythematosus (FaMaLE): a prospective cohort study for finding the molecular mechanisms behind pregnancy complications

IntroductionPregnant women with systemic lupus erythematosus (SLE) have an increased risk of maternal complications and adverse fetal outcomes. These include preeclampsia, preterm birth and fetal growth restriction. Interestingly, this increased risk persists in subsequent pregnancies, whereas it decreases in healthy women due to the development of maternal-fetal tolerance. As maternal-fetal tolerance is crucial for a healthy pregnancy, we hypothesize that its failure contributes to the increased risk of pregnancy complications in women with SLE. Therefore, we initiated the FaMaLE study to investigate the failure of maternal-fetal tolerance in pregnant women with SLE. Methods and analysisIn the FaMaLE study, women with SLE and healthy women are included in their first trimester of pregnancy (< 14 weeks gestational age (GA)) at Amsterdam UMC. Throughout the pregnancy, data on SLE disease activity, pregnancy course, and medication use are collected. Peripheral blood is collected once per trimester, within 48 hours before delivery and 5-12 weeks post-partum. In addition, the placenta is collected after delivery. Whole blood, peripheral blood mononuclear cells (PBMC) and placenta samples are freshly analyzed by flow cytometry to assess immune cell composition. The resulting data are analyzed in relation to SLE disease course, pregnancy course and pregnancy outcomes. Ethics and disseminationThe study has been approved by the Amsterdam UMC Medical Ethics Committee and all participating women will be asked to provide informed consent. The findings will be disseminated through peer-reviewed publications, presentations at scientific meetings and via patient organizations. STRENGTHS AND WEAKNESSES- A unique prospective longitudinal study design, featuring the collection of serum, plasma and PBMC throughout and after pregnancy, alongside placental cells and biopsies from the same participants. This is complemented by detailed clinical data on SLE disease course and pregnancy course, and outcomes. - Fresh flow cytometry analyses allow immediate assessment of cell composition in blood and placenta, without freeze/thawing effects - The study does not include pre-pregnancy collection of serum, plasma and PBMC; however detailed clinical data are collected during this period.