Dataset Information

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

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.

SUBMITTER: Han X

PROVIDER: S-EPMC6584811 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Publications

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

Han Xiaoyuan X Ghaemi Mohammad S MS Ando Kazuo K Peterson Laura S LS Ganio Edward A EA Tsai Amy S AS Gaudilliere Dyani K DK Stelzer Ina A IA Einhaus Jakob J Bertrand Basile B Stanley Natalie N Culos Anthony A Tanada Athena A Hedou Julien J Tsai Eileen S ES Fallahzadeh Ramin R Wong Ronald J RJ Judy Amy E AE Winn Virginia D VD Druzin Maurice L ML Blumenfeld Yair J YJ Hlatky Mark A MA Quaintance Cecele C CC Gibbs Ronald S RS Carvalho Brendan B Shaw Gary M GM Stevenson David K DK Angst Martin S MS Aghaeepour Nima N Gaudilliere Brice B

Frontiers in immunology 20190611

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-dim ...[more]

PMID: 31263463

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Project description:INTRODUCTION:This study aims to determine the association between temperature and preeclampsia and whether it is affected by seasonality and rural/urban lifestyle. METHODS:This cohort study included women who delivered at our medical center from 2004 to 2013 (31,101 women, 64,566 deliveries). Temperature values were obtained from a spatiotemporally resolved estimation model performing predictions at a 1×1km spatial resolution. In "Warm" pregnancies >50% of gestation occurred during the spring-summer period. In cold pregnancies >50% of gestation occurred during the fall and winter. Generalized estimating equation multivariable models were used to estimate the association between temperature and incidence of preeclampsia. RESULTS:1) The incidence of preeclampsia in at least one pregnancy was 7% (2173/64,566); 2) during "warm" pregnancies, an elevation of one IQR of the average temperature in the 1st or the 3rd trimesters was associated with an increased risk to develop preeclampsia [patients with Jewish ethnicity: 1st trimester: relative risk (RR) of 2.38(95%CI 1.50; 3.80), 3rd trimester 1.94(95%CI 1.34;2.81); Bedouins: 1st trimester: RR = 2.91(95%CI 1.98;4.28), 3rd trimester: RR = 2.37(95%CI 1.75;3.20)]; 3) In "cold" pregnancies, an elevation of one IQR of average temperature was associated with a lower risk to develop preeclampsia among patients with Bedouin-Arab ethnicity RR = 0.68 (95% CI 0.49-0.94) for 1st trimester and RR = 0.62 (95% CI 0.44-0.87) for 3rd trimester. CONCLUSIONS:1) Elevated averaged temperature during the 1st or 3rd trimesters in "warm" pregnancies confer an increased risk for the development of preeclampsia, especially in nomadic patients; 2) Of interest, during cold pregnancies, elevated averaged temperature was associated with a lower risk to develop preeclampsia for nomadic patients. 3) These findings suggest temperature might be associated with perturbations in maternal heat homeostasis resulting in reallocation of energy resources and their availability to the fetus that may increase the risk for preeclampsia. This observation is especially relevant in the context of global warming and its effects on maternal/fetal reproductive health.

Dataset Information

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

Publications

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

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