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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2019-06-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.01305/full |
| _version_ | 1818143133143138304 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Xiaoyuan Han |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T11:26:49Z |
| format | Article |
| id | doaj.art-d6c4dbcad99b424ba7d6e1e76d63d1d3 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-11T11:26:49Z |
| publishDate | 2019-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-d6c4dbcad99b424ba7d6e1e76d63d1d32022-12-22T01:08:59ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-06-011010.3389/fimmu.2019.01305450842Differential Dynamics of the Maternal Immune System in Healthy Pregnancy and PreeclampsiaXiaoyuan Han0Mohammad S. Ghaemi1Kazuo Ando2Laura S. Peterson3Edward A. Ganio4Amy S. Tsai5Dyani K. Gaudilliere6Ina A. Stelzer7Jakob Einhaus8Basile Bertrand9Natalie Stanley10Anthony Culos11Athena Tanada12Julien Hedou13Eileen S. Tsai14Ramin Fallahzadeh15Ronald J. Wong16Ronald J. Wong17Amy E. Judy18Virginia D. Winn19Maurice L. Druzin20Yair J. Blumenfeld21Mark A. Hlatky22Cecele C. Quaintance23Ronald S. Gibbs24Brendan Carvalho25Gary M. Shaw26Gary M. Shaw27David K. Stevenson28David K. Stevenson29Martin S. Angst30Nima Aghaeepour31Brice Gaudilliere32Department of Anesthesiology, Perioperative and Pain Medicine, School of Medicine, Stanford University, Palo Alto, CA, United StatesDepartment of Anesthesiology, Perioperative and Pain Medicine, School of Medicine, Stanford University, Palo Alto, CA, United StatesDepartment of Anesthesiology, Perioperative and Pain Medicine, School of Medicine, Stanford University, Palo Alto, CA, United StatesDepartment of Pediatrics, School of Medicine, Stanford University, Palo Alto, CA, United StatesDepartment of Anesthesiology, Perioperative and Pain Medicine, School of Medicine, Stanford University, Palo Alto, CA, United StatesDepartment of Anesthesiology, Perioperative and Pain Medicine, School of Medicine, Stanford University, Palo Alto, CA, United StatesDepartment of Surgery, School of Medicine, Stanford University, Palo Alto, CA, United StatesDepartment of Anesthesiology, Perioperative and Pain Medicine, School of Medicine, Stanford University, Palo Alto, CA, United StatesDepartment of Anesthesiology, Perioperative and Pain Medicine, School of Medicine, Stanford University, Palo Alto, CA, United StatesDepartment of Anesthesiology, Perioperative and Pain Medicine, School of Medicine, Stanford University, Palo Alto, CA, United StatesDepartment of Anesthesiology, Perioperative and Pain Medicine, School of Medicine, Stanford University, Palo Alto, CA, United StatesDepartment of Anesthesiology, Perioperative and Pain Medicine, School of Medicine, Stanford University, Palo Alto, CA, United StatesDepartment of Anesthesiology, Perioperative and Pain Medicine, School of Medicine, Stanford University, Palo Alto, CA, United StatesDepartment of Anesthesiology, Perioperative and Pain Medicine, School of Medicine, Stanford University, Palo Alto, CA, United StatesDepartment of Anesthesiology, Perioperative and Pain Medicine, School of Medicine, Stanford University, Palo Alto, CA, United StatesDepartment of Anesthesiology, Perioperative and Pain Medicine, School of Medicine, Stanford University, Palo Alto, CA, United StatesDepartment of Pediatrics, School of Medicine, Stanford University, Palo Alto, CA, United StatesMarch of Dimes Prematurity Research Center, School of Medicine, Stanford University, Palo Alto, CA, United StatesDepartment of Obstetrics and Gynecology, School of Medicine, Stanford University, Palo Alto, CA, United StatesDepartment of Obstetrics and Gynecology, School of Medicine, Stanford University, Palo Alto, CA, United StatesDepartment of Obstetrics and Gynecology, School of Medicine, Stanford University, Palo Alto, CA, United StatesDepartment of Obstetrics and Gynecology, School of Medicine, Stanford University, Palo Alto, CA, United StatesDepartment of Health Research and Policy, School of Medicine, Stanford University, Palo Alto, CA, United StatesMarch of Dimes Prematurity Research Center, School of Medicine, Stanford University, Palo Alto, CA, United StatesDepartment of Obstetrics and Gynecology, School of Medicine, Stanford University, Palo Alto, CA, United StatesDepartment of Anesthesiology, Perioperative and Pain Medicine, School of Medicine, Stanford University, Palo Alto, CA, United StatesDepartment of Pediatrics, School of Medicine, Stanford University, Palo Alto, CA, United StatesMarch of Dimes Prematurity Research Center, School of Medicine, Stanford University, Palo Alto, CA, United StatesDepartment of Pediatrics, School of Medicine, Stanford University, Palo Alto, CA, United StatesMarch of Dimes Prematurity Research Center, School of Medicine, Stanford University, Palo Alto, CA, United StatesDepartment of Anesthesiology, Perioperative and Pain Medicine, School of Medicine, Stanford University, Palo Alto, CA, United StatesDepartment of Anesthesiology, Perioperative and Pain Medicine, School of Medicine, Stanford University, Palo Alto, CA, United StatesDepartment of Anesthesiology, Perioperative and Pain Medicine, School of Medicine, Stanford University, Palo Alto, CA, United StatesPreeclampsia 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.https://www.frontiersin.org/article/10.3389/fimmu.2019.01305/fullpreeclampsiaimmunologymass cytometryPBMCpregnancy |
| spellingShingle | 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 Differential Dynamics of the Maternal Immune System in Healthy Pregnancy and Preeclampsia Frontiers in Immunology preeclampsia immunology mass cytometry PBMC pregnancy |
| title | Differential Dynamics of the Maternal Immune System in Healthy Pregnancy and Preeclampsia |
| title_full | Differential Dynamics of the Maternal Immune System in Healthy Pregnancy and Preeclampsia |
| title_fullStr | Differential Dynamics of the Maternal Immune System in Healthy Pregnancy and Preeclampsia |
| title_full_unstemmed | Differential Dynamics of the Maternal Immune System in Healthy Pregnancy and Preeclampsia |
| title_short | Differential Dynamics of the Maternal Immune System in Healthy Pregnancy and Preeclampsia |
| title_sort | differential dynamics of the maternal immune system in healthy pregnancy and preeclampsia |
| topic | preeclampsia immunology mass cytometry PBMC pregnancy |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.01305/full |
| work_keys_str_mv | AT xiaoyuanhan differentialdynamicsofthematernalimmunesysteminhealthypregnancyandpreeclampsia AT mohammadsghaemi differentialdynamicsofthematernalimmunesysteminhealthypregnancyandpreeclampsia AT kazuoando differentialdynamicsofthematernalimmunesysteminhealthypregnancyandpreeclampsia AT lauraspeterson differentialdynamicsofthematernalimmunesysteminhealthypregnancyandpreeclampsia AT edwardaganio differentialdynamicsofthematernalimmunesysteminhealthypregnancyandpreeclampsia AT amystsai differentialdynamicsofthematernalimmunesysteminhealthypregnancyandpreeclampsia AT dyanikgaudilliere differentialdynamicsofthematernalimmunesysteminhealthypregnancyandpreeclampsia AT inaastelzer differentialdynamicsofthematernalimmunesysteminhealthypregnancyandpreeclampsia AT jakobeinhaus differentialdynamicsofthematernalimmunesysteminhealthypregnancyandpreeclampsia AT basilebertrand differentialdynamicsofthematernalimmunesysteminhealthypregnancyandpreeclampsia AT nataliestanley differentialdynamicsofthematernalimmunesysteminhealthypregnancyandpreeclampsia AT anthonyculos differentialdynamicsofthematernalimmunesysteminhealthypregnancyandpreeclampsia AT athenatanada differentialdynamicsofthematernalimmunesysteminhealthypregnancyandpreeclampsia AT julienhedou differentialdynamicsofthematernalimmunesysteminhealthypregnancyandpreeclampsia AT eileenstsai differentialdynamicsofthematernalimmunesysteminhealthypregnancyandpreeclampsia AT raminfallahzadeh differentialdynamicsofthematernalimmunesysteminhealthypregnancyandpreeclampsia AT ronaldjwong differentialdynamicsofthematernalimmunesysteminhealthypregnancyandpreeclampsia AT ronaldjwong differentialdynamicsofthematernalimmunesysteminhealthypregnancyandpreeclampsia AT amyejudy differentialdynamicsofthematernalimmunesysteminhealthypregnancyandpreeclampsia AT virginiadwinn differentialdynamicsofthematernalimmunesysteminhealthypregnancyandpreeclampsia AT mauriceldruzin differentialdynamicsofthematernalimmunesysteminhealthypregnancyandpreeclampsia AT yairjblumenfeld differentialdynamicsofthematernalimmunesysteminhealthypregnancyandpreeclampsia AT markahlatky differentialdynamicsofthematernalimmunesysteminhealthypregnancyandpreeclampsia AT cecelecquaintance differentialdynamicsofthematernalimmunesysteminhealthypregnancyandpreeclampsia AT ronaldsgibbs differentialdynamicsofthematernalimmunesysteminhealthypregnancyandpreeclampsia AT brendancarvalho differentialdynamicsofthematernalimmunesysteminhealthypregnancyandpreeclampsia AT garymshaw differentialdynamicsofthematernalimmunesysteminhealthypregnancyandpreeclampsia AT garymshaw differentialdynamicsofthematernalimmunesysteminhealthypregnancyandpreeclampsia AT davidkstevenson differentialdynamicsofthematernalimmunesysteminhealthypregnancyandpreeclampsia AT davidkstevenson differentialdynamicsofthematernalimmunesysteminhealthypregnancyandpreeclampsia AT martinsangst differentialdynamicsofthematernalimmunesysteminhealthypregnancyandpreeclampsia AT nimaaghaeepour differentialdynamicsofthematernalimmunesysteminhealthypregnancyandpreeclampsia AT bricegaudilliere differentialdynamicsofthematernalimmunesysteminhealthypregnancyandpreeclampsia |