SUPR
cfDNA methylation profiling
Dnr:

sens2023033

Type:

NAISS SENS

Principal Investigator:

Juha Kere

Affiliation:

Karolinska Institutet

Start Date:

2024-02-27

End Date:

2025-03-01

Primary Classification:

30220: Obstetrics, Gynaecology and Reproductive Medicine

Webpage:

Allocation

Abstract

Pre-eclampsia is a serious pregnancy complication threatening the well-being of both the mother and the fetus, and worldwide one of the leading causes of mortality among pregnant women. The disorder starts typically after week 20 of pregnancy. The project has a solid basis on our published results and previous literature. An essential mechanism of pre-eclampsia involves the compromised genetic ability of the fetus to protect itself against maternal immune surveillance and attack toward the foreign body of cells (trophoblasts in placenta). This results essentially in a slow autoimmune-type rejection with a cytokine profile reminiscent of systemic lupus. The aim of our project is to develop blood-sample based sensitive methods to predict and diagnose threatening pre-eclampsia weeks before the onset of symptoms. We aim also to distinguish between milder and more severe cases before the full-blown clinical phenotype. We use methods based on sensitive RNA (STRT seq) and DNA (TAC-seq, Nanopore seq) based analyses of mother’s circulating white blood cells as well as liquid DNA molecules (cell-free DNA, cfDNA) originating from damaged trophoblasts in mother’s plasma. These combined methods will detect signs of the immune attack/placental damage earlier than any currently available methods. The project is based on our clinical sample collection from Huddinge Hospital (registered as PRECAMP) and our in-house developed assays set up at our laboratory at KI/BioNut. Based on the early diagnosis, each patient can receive the most appropriate management. Clinical relevance of the project is immediate and very high.