Data from: Systemic immune dysregulation in hypertensive disorders of pregnancy persists years after delivery
Data files
Mar 02, 2026 version files 67.63 GB
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AP_FCSfiles.zip
18.01 GB
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EPOCH_Histone.csv
5.30 MB
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EPOCH_processed.csv
42.83 MB
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ML_FCSfiles.zip
33.35 GB
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outcomeAP.csv
543 B
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outcomeML.csv
1.17 KB
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outcomePP.csv
647 B
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PP_FCSfiles.zip
16.23 GB
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README.md
6.65 KB
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Severity.xlsx
20.15 KB
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SF1_PenalizationMatrix.xlsx
20.37 KB
Abstract
Background: Hypertensive disorders of pregnancy (HDP), including preeclampsia and gestational hypertension, are associated with an increased risk of cardiovascular disease (CVD) later in life. Mechanisms that link HDP to CVD, however, remain unclear.
Methods: We used a high-dimensional single-cell mass cytometry approach to profile the distribution and functional responses of maternal immune cells in three groups of HDP cases and normotensive controls: antepartum, postpartum, and midlife. We used multivariable sparse modeling to distinguish HDP cases from controls.
Results: We accurately distinguished HDP cases from controls at all three study timepoints, with area under the receiver operator characteristic (AUROC) values of 0.814 for the antepartum group, 0.757 for the postpartum group, and 0.692 for the midlife group. We identified a persistent immune dysregulation signal among cases at all three timepoints, characterized by increased B cell frequency and decreased pSTAT3 response upon cytokine stimulation in classical monocytes.
Conclusions: Persistent immune dysregulation among cases suggests that HDP has a lasting impact on the immune system, which may contribute to elevated long-term risk of CVD development.
Dataset DOI: 10.5061/dryad.7m0cfxq7w
Description of the data and file structure
Goal:
Identify whether the immune system is dysgregulated in case with hypertensive disorders of pregnancy by analysing the distribution and function of the maternal immune system using mass cytometry across three groups: antepartum, postpartum, and midlife.
Mass cytometry:
Whole blood samples were collected into sodium-heparinized vacutainers. Blood aliquots were stimulated for 15 minutes at 37°C with either LPS (1μg/mL), IL-18 (100ng/mL), a cocktail containing IL-2, IL-4, and IL-6 (100ng/mL each), or PBS (unstimulated condition). Samples were with Proteomic Stabilizer (SmartTube) for 10 minutes and stored at -80°C until further processing for mass cytometry.
Cell frequencies are reported as a percentage of mononuclear cells, with the exception of granulocyte subsets, which are reported as a percentage of singlet leukocytes. Median signal intensity of phosphosignaling proteins and functional markers are arcsinh transformed (arcsinh(x/5)). Endogenous signaling/functional activity is assessed in unstimulated cells, while response to stimulation is expressed as the arcsinh-transformed ratio relative to the endogenous response, i.e., the difference in arcsinh-transformed signal intensity between the stimulated and unstimulated condition.
A penalization matrix, based on prior mechanistic immunological knowledge of receptor-specific canonical signaling pathways, is applied before continuing further analysis.
Further information and requests for resources and reagents should be directed to an will be fulfilled by the lead contact, Brice Gaudillière (gbrice@stanford.edu)
Files and variables
File: SF1_PenalizationMatrix.xlsx
Description: Penalization matrix used to penalize the mass cytometry data. This penalization matrix is based on prior mechanistic immunological knowledge of receptor-specific canonical signaling pathways.
- File consists of 4 tabs, reflecting the stimulation used: Unstim, LPS, IL246, and IL18
- Each tab contains a data matrix where the rows are cell types, and the columns are functional markers
- A value of 1 in the data matrix indicates features (combination of cell type and functional marker) that were included in the analysis, while a value of 0 indicates those that were excluded
File: AP_FCSfiles.zip
Description: Raw FCS files from the mass cytometry measurements for the AP cohort
File: ML_FCSfiles.zip
Description: Raw FCS files from the mass cytometry measurements for the ML cohort
File: PP_FCSfiles.zip
Description: Raw FCS files from the mass cytometry measurements for the PP cohort
File: Severity.xlsx
Description: File containing severity information regarding the cases and controls. The file is split up into 4 tabs: Abbreviations, AP, PP, and ML. The AP, PP, and ML contain the severity data for each cohort.
Variables: the following variables are present in the demographics data
- Subject ID = sample ID
- Case/Control = indicates whether the sample ID is a case or a control
- 1=AP or PP sample, 2=both AP and PP sample = indicates whether the sample is only present in the AP or PP cohort, or in both
- gestational age @ Sampling (range in weeks) = gestational age, in weeks, at time of sampling. This time-related variable is reflected as a range: ≤27, 28-31, 32-35, or ≥36
- gestational age @ Onset of Hypertensive Disorder = gestational age at time of onset of the hypertensive disorder of pregnancy. This variable is reflected as either early-onset (≤34 weeks) or late-onset (>34 weeks)
- Severity Measures = indicates how severe the participant's hypertensive disorder of pregnancy was
- Time since Delivery @ sampling (range in weeks) = number of weeks since delivery at the time of sampling. This time-related variable is reflected as a range: 0-8, 9-16, 17-24, 25-32, 33-40, 41-48, or >49
- Years since last delivery, range = number of years since last delivery at time of sampling. This time-related variable is reflected as a range: <2, 2-5, 5-10, 10-15, or >15
File: EPOCH_Histone.csv
Description: Arcsinh transformed median marker expression of histone markers.
Variables
- population: cell subset
- reagent: histone marker
- sampleID: sampleID
- time: whether the sample is in the AP, PP, or ML cohort
- stimulation: stimulation condition
- Cohort: from which cohort sample came
- median: arcsinh-transformed median marker expression
File: EPOCH_processed.csv
Description: Frequencies and processed functional/phosphosignaling responses of the mass cytometry dataset.
Variables
- population: cell subset
- reagent: functional/phosphosignaling marker or frequency label
- sampleID: sampleID
- time: whether the sample is in the AP, PP, or ML cohort
- Cohort: from which cohort sample came
- stimulation: stimulation condition
- feature: processed median marker expression or frequency
File: outcomeAP.csv
Description: File indicating which samples were used in the analysis, and indicating whether a certain individual is a case (Group = 1) or control (Group = 0).
Variables
- sampleID: sampleID
- Group: Case = 1, Control = 0
File: outcomeML.csv
Description: File indicating which samples were used in the analysis, and indicating whether a certain individual is a case (Group = 1) or control (Group = 0).
Variables
- sampleID: sampleID
- Group: Case = 1, Control = 0
File: outcomePP.csv
Description: File indicating which samples were used in the analysis, and indicating whether a certain individual is a case (Group = 1) or control (Group = 0).
Variables
- sampleID: sampleID
- Group: Case = 1, Control = 0
Code/software
Multivariate modeling is done using the Stabl algorithm: Hédou et al, Nat Biotechnol, 2024 (PMID: 38168992).
Further information and requests for resources and reagents should be directed to an will be fulfilled by the lead contact, Brice Gaudillière (gbrice@stanford.edu).
Human subjects data
This study was approved by the Stanford University Institutional Review Board, and all participants provided written informed consent, including consent to sharing of de-identified data in public databases. All data is de-identified.