Failing maternal-fetal tolerance in SLE: finding the molecular mechanisms behind pregnancy complications

Concept

Pregnant women with systemic lupus erythematosus (SLE) have an increased risk of maternal complications and adverse fetal outcomes. To better predict and prevent adverse outcomes of SLE pregnancies, it is crucial to understand the underlying biological processes.
Failing maternal-fetal tolerance is thought to play an important role in the increased risk for pregnancy complications in SLE patients. However, it is unknown which mechanisms mediate maternal-fetal tolerance and how the dysregulated immune system in SLE affects this process.
This study will identify potential therapeutic targets based on the mechanisms underlying failing maternal-fetal tolerance in SLE. Furthermore, it will deliver potential biomarkers for early detection of developing complications. Thereby, the findings in this study will contribute to the improvement of SLE pregnancy outcomes with benefits for both mother and child.

Facts and Figures

Project Lead
W Dankers
Amsterdam UMC
wendy.dankers@monash.edu
FOREUM research grant: € 200’000
2021 - 2024

Meet the Team

W Dankers
Amsterdam UMC
L G M van Baarsen
Amsterdam UMC
I E M Bultink
Amsterdam UMC
M de Boer
Amsterdam UMC
K Cramer
Amsterdam UMC
D Rohrich
Amsterdam UMC

Objectives

The overall objective of this research is to delineate which cellular processes mediate failing maternal-fetal tolerance in SLE patients. Furthermore, the aim is to define potential biomarkers for earlier detection of complications. The group hypothesises that the abnormally regulated immune system in SLE patients causes aberrant interactions at the maternal-fetal interface, resulting in failure of immunological tolerance.
AIM 1: Compare the cellular distribution and activation state of placental cells from women with SLE with healthy women
AIM 2: Analyze cell-cell interactions at the maternal-fetal interface
AIM 3: Identify peripheral blood biomarkers associated with failing maternal-fetal tolerance

Patient Voice

This study greatly advances our understanding of the processes leading to pregnancy complications in SLE patients. This is a crucial first step in better predicting and improving
pregnancy outcomes for SLE patients, for example by monitoring the cells identified in the final part of our project in the blood of women with SLE. This work will also be a benefit for future research to develop intervention strategies to reduce pregnancy complications.

Goals/Milestones

Milestone 1: ethics approved (Year 1, end of Q2)
Milestone 2: all patients included (Year 2, end of Q4)
Milestone 3: scRNA sequencing done (Year 2, end of Q2)
Milestone 4: optimization and validation of organoid models – publication 1 (Year 1, end of Q4)
Milestone 5: mechanisms and biomarkers identified – publication 2 (Year 3, end of Q4)