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Maternal blood: a window into the neonatal immune system
Abstract Number: GM-06
Abstract Type: Original Research
Introduction: Peripartum infection is a leading cause of morbidity and mortality for mothers and their newborns. Determining maternal immune signatures that predict neonatal susceptibility to infection will facilitate risk stratification and earlier treatment. This study used high dimensional mass cytometry to comprehensively interrogate the immune systems of neonates and their mothers to identify functional immune responses in maternal blood uniquely associated with their neonate.
Methods: Umbilical cord-blood (n=10) and maternal peripheral blood (n=10) samples were stained with 21 cell-surface and 15 intracellular functional markers at basal state and after stimulation with exogenous ligands (LPS; IL-2, IL-6, GM-CSF, and INFa). An unsupervised hierarchical clustering algorithm (SCAFFOLD) was used to group immune cells by similarity of cell-surface markers, and visually present their characteristics via force-directed layout. Correlation of paired and unpaired neonatal and maternal immune responses followed by principal component analysis was performed and significant features (Bonferroni-corrected p <0.05) were identified.
Results: Superimposable maps of maternal and neonatal immune systems highlighted phenotypic differences across adaptive and innate cell subsets reflecting the tolerogenic bias of the neonatal compared to maternal immune system. Functional interrogation of single-cell intracellular signaling responses identified 81 immune features that distinguish neonatal and maternal immune response. These include dampened neonatal P38 MAPK signaling response in innate immune cells, and exacerbated STAT3 and STAT5 signaling responses in adaptive cell subsets. Analysis of paired and unpaired comparisons of functional responses revealed a subset of 27 unique immune features that significantly distinguish maternal and neonatal pairs but not the average population (Fig 1).
Conclusions: This study presents a comprehensive map of the neonatal and maternal immune systems, and highlights functional immune features tightly associated between mother and neonate. The findings provide mechanistic data for the development of predictive models of the neonatal immune response based on a maternal blood test. Tests that predict neonatal susceptibility to infection have the potential to facilitate risk stratification and aid clinical decisions for peripartum neonatal inflammatory states in preterm labor, premature rupture of membranes and chorioamnionitis.