Skip to main content
Article
Differential dynamics of the maternal immune system in healthy pregnancy and preeclampsia
Frontiers in Immunology
  • Xiaoyuan Han, Stanford University
  • Mohammad Sajjad Ghaemi, Stanford University
  • Kazuo Ando, Stanford University
  • Laura S. Peterson, Stanford University
  • Edward A. Ganio, Stanford University
  • Amy S. Tsai, Stanford University
  • Dyani K. Gaudilliere, Stanford University
  • Ina A. Stelzer, Stanford University
  • Jakob Einhaus, Stanford University
  • Basile Bertrand, Stanford University
  • Natalie Stanley, Stanford University
  • Anthony Culos, Stanford University
  • Athena Tanada, Stanford University
  • Julien Hedou, Stanford University
  • Eileen S. Tsai, Stanford University
  • Ramin Fallahzadeh, Stanford University
  • Ronald J. Wong, Stanford University
  • Amy E. Judy, Stanford University
  • Virginia D. Winn, Stanford University
  • Maurice L. Druzin, Stanford University
  • Yair J. Blumenfeld, Stanford University
  • Mark A. Hlatky, Stanford University
  • Cecele C. Quaintance, Stanford University
  • Ronald S. Gibbs, Stanford University
  • Brendan Carvalho, Stanford University
  • Gary M. Shaw, Stanford University
  • David K. Stevenson, Stanford University
  • Martin S. Angst, Stanford University
  • Nima Aghaeepour, Stanford University
Department
Biomedical Sciences
Document Type
Article
DOI
10.3389/fimmu.2019.01305
Publication Date
1-1-2019
Abstract

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, p = 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.

Creative Commons License
Creative Commons Attribution 4.0 International
Citation Information
Xiaoyuan Han, Mohammad Sajjad Ghaemi, Kazuo Ando, Laura S. Peterson, et al.. "Differential dynamics of the maternal immune system in healthy pregnancy and preeclampsia" Frontiers in Immunology Vol. 10 Iss. JUN (2019) ISSN: 1664-3224
Available at: http://works.bepress.com/xiaoyuan-han/41/