Frontiers in Immunology (Jun 2019)
Differential Dynamics of the Maternal Immune System in Healthy Pregnancy and Preeclampsia
- Xiaoyuan Han,
- Mohammad S. Ghaemi,
- Kazuo Ando,
- Laura S. Peterson,
- Edward A. Ganio,
- Amy S. Tsai,
- Dyani K. Gaudilliere,
- Ina A. Stelzer,
- Jakob Einhaus,
- Basile Bertrand,
- Natalie Stanley,
- Anthony Culos,
- Athena Tanada,
- Julien Hedou,
- Eileen S. Tsai,
- Ramin Fallahzadeh,
- Ronald J. Wong,
- Ronald J. Wong,
- Amy E. Judy,
- Virginia D. Winn,
- Maurice L. Druzin,
- Yair J. Blumenfeld,
- Mark A. Hlatky,
- Cecele C. Quaintance,
- Ronald S. Gibbs,
- Brendan Carvalho,
- Gary M. Shaw,
- Gary M. Shaw,
- David K. Stevenson,
- David K. Stevenson,
- Martin S. Angst,
- Nima Aghaeepour,
- Brice Gaudilliere
Affiliations
- Xiaoyuan Han
- Department of Anesthesiology, Perioperative and Pain Medicine, School of Medicine, Stanford University, Palo Alto, CA, United States
- Mohammad S. Ghaemi
- Department of Anesthesiology, Perioperative and Pain Medicine, School of Medicine, Stanford University, Palo Alto, CA, United States
- Kazuo Ando
- Department of Anesthesiology, Perioperative and Pain Medicine, School of Medicine, Stanford University, Palo Alto, CA, United States
- Laura S. Peterson
- Department of Pediatrics, School of Medicine, Stanford University, Palo Alto, CA, United States
- Edward A. Ganio
- Department of Anesthesiology, Perioperative and Pain Medicine, School of Medicine, Stanford University, Palo Alto, CA, United States
- Amy S. Tsai
- Department of Anesthesiology, Perioperative and Pain Medicine, School of Medicine, Stanford University, Palo Alto, CA, United States
- Dyani K. Gaudilliere
- Department of Surgery, School of Medicine, Stanford University, Palo Alto, CA, United States
- Ina A. Stelzer
- Department of Anesthesiology, Perioperative and Pain Medicine, School of Medicine, Stanford University, Palo Alto, CA, United States
- Jakob Einhaus
- Department of Anesthesiology, Perioperative and Pain Medicine, School of Medicine, Stanford University, Palo Alto, CA, United States
- Basile Bertrand
- Department of Anesthesiology, Perioperative and Pain Medicine, School of Medicine, Stanford University, Palo Alto, CA, United States
- Natalie Stanley
- Department of Anesthesiology, Perioperative and Pain Medicine, School of Medicine, Stanford University, Palo Alto, CA, United States
- Anthony Culos
- Department of Anesthesiology, Perioperative and Pain Medicine, School of Medicine, Stanford University, Palo Alto, CA, United States
- Athena Tanada
- Department of Anesthesiology, Perioperative and Pain Medicine, School of Medicine, Stanford University, Palo Alto, CA, United States
- Julien Hedou
- Department of Anesthesiology, Perioperative and Pain Medicine, School of Medicine, Stanford University, Palo Alto, CA, United States
- Eileen S. Tsai
- Department of Anesthesiology, Perioperative and Pain Medicine, School of Medicine, Stanford University, Palo Alto, CA, United States
- Ramin Fallahzadeh
- Department of Anesthesiology, Perioperative and Pain Medicine, School of Medicine, Stanford University, Palo Alto, CA, United States
- Ronald J. Wong
- Department of Pediatrics, School of Medicine, Stanford University, Palo Alto, CA, United States
- Ronald J. Wong
- March of Dimes Prematurity Research Center, School of Medicine, Stanford University, Palo Alto, CA, United States
- Amy E. Judy
- Department of Obstetrics and Gynecology, School of Medicine, Stanford University, Palo Alto, CA, United States
- Virginia D. Winn
- Department of Obstetrics and Gynecology, School of Medicine, Stanford University, Palo Alto, CA, United States
- Maurice L. Druzin
- Department of Obstetrics and Gynecology, School of Medicine, Stanford University, Palo Alto, CA, United States
- Yair J. Blumenfeld
- Department of Obstetrics and Gynecology, School of Medicine, Stanford University, Palo Alto, CA, United States
- Mark A. Hlatky
- Department of Health Research and Policy, School of Medicine, Stanford University, Palo Alto, CA, United States
- Cecele C. Quaintance
- March of Dimes Prematurity Research Center, School of Medicine, Stanford University, Palo Alto, CA, United States
- Ronald S. Gibbs
- Department of Obstetrics and Gynecology, School of Medicine, Stanford University, Palo Alto, CA, United States
- Brendan Carvalho
- Department of Anesthesiology, Perioperative and Pain Medicine, School of Medicine, Stanford University, Palo Alto, CA, United States
- Gary M. Shaw
- Department of Pediatrics, School of Medicine, Stanford University, Palo Alto, CA, United States
- Gary M. Shaw
- March of Dimes Prematurity Research Center, School of Medicine, Stanford University, Palo Alto, CA, United States
- David K. Stevenson
- Department of Pediatrics, School of Medicine, Stanford University, Palo Alto, CA, United States
- David K. Stevenson
- March of Dimes Prematurity Research Center, School of Medicine, Stanford University, Palo Alto, CA, United States
- Martin S. Angst
- Department of Anesthesiology, Perioperative and Pain Medicine, School of Medicine, Stanford University, Palo Alto, CA, United States
- Nima Aghaeepour
- Department of Anesthesiology, Perioperative and Pain Medicine, School of Medicine, Stanford University, Palo Alto, CA, United States
- Brice Gaudilliere
- Department of Anesthesiology, Perioperative and Pain Medicine, School of Medicine, Stanford University, Palo Alto, CA, United States
- DOI
- https://doi.org/10.3389/fimmu.2019.01305
- Journal volume & issue
-
Vol. 10
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.
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