Differential Dynamics of the Maternal Immune System in Healthy Pregnancy and Preeclampsia

Preeclampsia is one of the most severe pregnancy complications and a leading cause of maternal death. However, early diagnosis of preeclampsia remains a clinical challenge. Alterations in the normal immune adaptations necessary for the maintenance of a healthy pregnancy are central features of preec...

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Published in:Frontiers in immunology Vol. 10; p. 1305
Main Authors: Han, Xiaoyuan, Ghaemi, Mohammad S., Ando, Kazuo, Peterson, Laura S., Ganio, Edward A., Tsai, Amy S., Gaudilliere, Dyani K., Stelzer, Ina A., Einhaus, Jakob, Bertrand, Basile, Stanley, Natalie, Culos, Anthony, Tanada, Athena, Hedou, Julien, Tsai, Eileen S., Fallahzadeh, Ramin, Wong, Ronald J., Judy, Amy E., Winn, Virginia D., Druzin, Maurice L., Blumenfeld, Yair J., Hlatky, Mark A., Quaintance, Cecele C., Gibbs, Ronald S., Carvalho, Brendan, Shaw, Gary M., Stevenson, David K., Angst, Martin S., Aghaeepour, Nima, Gaudilliere, Brice
Format: Journal Article
Language:English
Published: Switzerland Frontiers Media S.A 11.06.2019
Subjects:
Adaptive Immunity
Adult
Case-Control Studies
Cohort Studies
Female
Flow Cytometry
Humans
Immunity, Innate
Immunoassay
Immunology
Inflammation - blood
Inflammation - complications
Inflammation - immunology
mass cytometry
Models, Immunological
PBMC
Pre-Eclampsia - blood
Pre-Eclampsia - diagnosis
Pre-Eclampsia - immunology
preeclampsia
pregnancy
Pregnancy - blood
Pregnancy - immunology
Prospective Studies
Signal Transduction - immunology
T-Lymphocyte Subsets - immunology
mass cytometry
preeclampsia
PBMC
immunology
pregnancy
ISSN:1664-3224, 1664-3224
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Summary:Preeclampsia is one of the most severe pregnancy complications and a leading cause of maternal death. However, early diagnosis of preeclampsia remains a clinical challenge. Alterations in the normal immune adaptations necessary for the maintenance of a healthy pregnancy are central features of preeclampsia. However, prior analyses primarily focused on the static assessment of select immune cell subsets have provided limited information for the prediction of preeclampsia. Here, we used a high-dimensional mass cytometry immunoassay to characterize the dynamic changes of over 370 immune cell features (including cell distribution and functional responses) in maternal blood during healthy and preeclamptic pregnancies. We found a set of eight cell-specific immune features that accurately identified patients well before the clinical diagnosis of preeclampsia (median area under the curve (AUC) 0.91, interquartile range [0.82-0.92]). Several features recapitulated previously known immune dysfunctions in preeclampsia, such as elevated pro-inflammatory innate immune responses early in pregnancy and impaired regulatory T (Treg) cell signaling. The analysis revealed additional novel immune responses that were strongly associated with, and preceded the onset of preeclampsia, notably abnormal STAT5ab signaling dynamics in CD4 T cell subsets (AUC 0.92, = 8.0E-5). These results provide a global readout of the dynamics of the maternal immune system early in pregnancy and lay the groundwork for identifying clinically-relevant immune dysfunctions for the prediction and prevention of preeclampsia.
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This article was submitted to Immunological Tolerance and Regulation, a section of the journal Frontiers in Immunology
Edited by: Helen Marie McGuire, University of Sydney, Australia
These authors have contributed equally to this work
Reviewed by: Frederic Sierro, Australian Nuclear Science and Technology Organisation, Australia; Peter Hsu, Children's Hospital at Westmead, Australia
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2019.01305