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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.

Biorxiv : the Preprint Server for Biology
|December 15, 2025
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), including preeclampsia and gestational hypertension, increase the risk of later-life cardiovascular disease (CVD).
  • 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 HDP compared to normotensive controls.
  • To identify potential immune system dysregulations that persist over time and may link HDP to long-term CVD risk.

Main Methods:

  • Employed high-dimensional single-cell mass cytometry to analyze maternal immune cells.
  • Sampled women antepartum, postpartum, and in midlife (several years postpartum).
  • Utilized multivariable sparse modeling to differentiate HDP cases from controls.

Main Results:

  • Successfully distinguished HDP cases from controls across all timepoints with significant accuracy (AUROC 0.692–0.814).
  • Revealed distinct immune signatures at each timepoint, indicating dynamic immune dysregulation.
  • Identified a persistent immune dysregulation in HDP cases, marked by increased B cells and altered monocyte responses.

Conclusions:

  • Persistent immune dysregulation following HDP may be a key factor contributing to the elevated long-term risk of cardiovascular disease.
  • Understanding these immune alterations offers potential targets for CVD prevention in women with HDP history.
Abstract

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