Preeclampsia-induced cardiovascular diseases: identification of specific immune markers using Infinity Flow

Preeclampsia (PE) is among the leading causes of maternal morbidity and mortality during pregnancy and increases the mothers’ risk of developing cardiovascular diseases later in life. The pathogenesis underlying this risk is still largely unknown. Therefore, we aimed to utilize high-dimensional analyses to reveal the complexity of the immune cell microenvironment underlying PE. PBMCs isolated from six healthy pregnant women from the longitudinal pregnancy study PRINCE (PRenatal IdeNtification of Children’s HEalth) and six pregnant women diagnosed with PE (PRINCECardio) were analysed by Infinity Flow, a novel screening approach combining conventional flow cytometry with machine learning, to assess the differential expression of 361 immune markers on protein level. Using a dimension reduction technique we created a UMAP showing the main CD3 T cell subpopulations, CD4, CD8 and γδ T cells. Within each cluster, we could identified variousmarkers that were significantly increased in pregnancies with PE, e.g. CD58 and CD258 being upregulated in all subclusters, whereas CD95 and CD29 were specifically increased in CD4 T cells.The Fas receptor (CD95) has been linked to the pathogenesis of cardiovascular diseases, suggesting a causal link between the pathophysiology of PE and subsequent cardiovascular diseases. Further, CD58 (lymphocyte function-associated antigen (LFA)-3) and CD258 (tumor necrosis factor superfamily member (TNFSF)-14) are associated with T cell activation and CD29 (integrin β1) expression on T cells has been linked to a cytotoxic phenotype which could account for cardiovascular damage triggered by immunological challenges during PE. However, our preliminary results need to be verified on a larger cohort.