Article Text
PDF
Abstract
Objective Pregnant women with systemic lupus erythematosus (SLE) have an increased risk of maternal complications and adverse fetal outcomes, like 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. Since 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 failing maternal-fetal tolerance in pregnant women with SLE.
Methods In the FaMaLE study, healthy women and women with SLE are included in their first trimester of pregnancy (<14 weeks gestational age (GA)) at Amsterdam UMC. Peripheral blood is collected once every trimester, within 48 hours before delivery and 5–12 weeks after delivery. Furthermore, the placenta is collected after delivery. Whole blood, peripheral blood mononuclear cells (PBMC) and placenta are freshly analyzed by flow cytometry.
Results First we set up a protocol for obtaining single-cell suspensions containing both immune cells and stromal cells from the placental basal plate and chorioamniotic membranes. Furthermore, we designed 5 flow cytometry panels to freshly analyze composition of placental cells, PBMC and whole blood. Currently 19 SLE patients are included in the study, of whom 15 have delivered (6 with complications) and 11 completed the study. Preliminary analysis of these 11 patients revealed a decreased CD4/CD8 ratio in the blood throughout and after pregnancy in women who experienced pregnancy complications. Furthermore, we found a decreased trophoblast/stromal cell ratio in the placenta of these patients.
Levels of OCP, OHP and OFP in SLE patients during pregnancy and in comparison to controls. Red circles represent patients with preeclampsia. C- control pregnant women without preeclampsia, C+PE control pregnant women with preeclampsia, T1 – first trimester during pregnancy in SLE patients, T3 – third trimester during pregnancy in SLE patients. 25th and 75th percentile of reference range of respective variable in healthy non-pregnant individuals
Conclusions In conclusion, we designed a workflow to study blood and placenta in SLE patients with and without pregnancy complications. In preliminary analysis we found significant differences in blood and placenta, which require validation in the rest of the cohort (total 18 healthy controls and 60 SLE patients). These data will provide novel insights into the development and failure of maternal-fetal tolerance, and thereby into pregnancy complications in women with SLE.
Acknowledgements This project was funded by FOREUM, NVLE Foundation, Amsterdam UMC, and the Amsterdam Reproduction and Development Institute.
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ .