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Systemic immune dysregulation in hypertensive disorders of pregnancy persists years after delivery

Maximilian Sabayev1,2, Edward A Ganio1, Ina A Stelzer1,3

  • 1Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, United States.

Frontiers in Immunology
|February 23, 2026
PubMed

Insights

Hypertensive disorders of pregnancy (HDP) are linked to future cardiovascular disease (CVD). Persistent immune system changes in women with HDP history may explain this increased long-term CVD risk.

Area of Science:

  • Immunology
  • Cardiovascular Health
  • Reproductive Medicine

Background:

  • Hypertensive disorders of pregnancy (HDP), such as preeclampsia and gestational hypertension, are known risk factors for developing cardiovascular disease (CVD) later in life.
  • The precise biological mechanisms connecting HDP to subsequent CVD remain incompletely understood.

Purpose of the Study:

  • To investigate the immune cell profiles and functional responses in women with and without a history of HDP across different life stages.
  • To identify potential immune signatures associated with HDP that may persist and contribute to long-term CVD risk.

Main Methods:

  • Utilized high-dimensional single-cell mass cytometry to analyze maternal immune cell distribution and function.
  • Employed multivariable sparse modeling to differentiate HDP cases from normotensive controls at antepartum, postpartum, and midlife timepoints.

Main Results:

  • Successfully distinguished HDP cases from controls with high accuracy (AUROC 0.692–0.814) across all study phases.
  • Revealed distinct immune signatures unique to each timepoint, indicating dynamic immune dysregulation.
  • Identified a persistent immune dysregulation signal in HDP cases, characterized by increased B cell frequency and altered monocyte responses to cytokine stimulation.

Conclusions:

  • Persistent immune dysregulation following HDP may be a key factor contributing to the elevated long-term risk of cardiovascular disease development in affected women.
  • Understanding these immune alterations offers potential targets for early detection and intervention strategies to mitigate future CVD risk.
Abstract

Keywords:
CyTOFhypertensive disorders of pregnancyimmunitymass cytometrypreeclampsiapregnancy

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