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Publications

Journal Article Ppublish

PubMed: 39821970 DOI: 10.1002/eji.202451386

Similar Spatial Expression of Immune-Related Proteins in SARS-CoV-2 Placentitis and Chronic Histiocytic Intervillositis.

Eur J Immunol 55(1):e202451386

Authors: Michelle Broekhuizen, Marie-Louise van der Hoorn, Disha Vadgama, Michael Eikmans, Bojou J Neecke, Johannes J Duvekot, Pieter Fraaij, Irwin K M Reiss, Dana A M Mustafa, Lotte E van der Meeren, Sam Schoenmakers

Affiliations

  • Division of Neonatology, Department of Neonatal and Pediatric Intensive Care, Erasmus MC, Rotterdam, The Netherlands.
  • Division of Pharmacology and Vascular Medicine, Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
  • Department of Obstetrics and Gynecology, Leiden University Medical Center, Leiden, The Netherlands.
  • Department of Pathology, Erasmus MC, Rotterdam, The Netherlands.
  • Department of Immunology, Leiden University Medical Center, Leiden, Netherlands.
  • Department of Pathology, Pathan, Rotterdam, The Netherlands.
  • Department of Obstetrics and Gynecology, Erasmus MC, Rotterdam, The Netherlands.
  • Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands.
  • Division Infectious Diseases and Immunology, Department of Pediatrics, Erasmus MC, Rotterdam, The Netherlands.
  • Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the placenta can lead to fetal distress and demise, characterized by severe trophoblast necrosis, chronic histiocytic intervillositis (CHI), and massive perivillous fibrin deposition. We aimed to uncover spatial immune-related protein changes in SARS-CoV-2 placentitis compared with CHI placentas and uncomplicated pregnancies to gain insight into the underlying pathophysiological mechanisms. Placentas were retrospectively collected from cases with SARS-CoV-2 placentitis resulting in fetal distress/demise (n = 9), CHI (n = 9), and uncomplicated term controls (n = 9). The expression of 53 immune-related proteins was quantified using GeoMx Digital Spatial Profiler in three separate compartments: villi (fetal compartment), intervillous space, and decidua (both maternal compartments). Compared with controls, SARS-CoV-2 placentitis and CHI both displayed differentially expressed proteins in the intervillous space only, including upregulation of myeloid markers (e.g., CD40, CD11c, CD68, CD163). Specifically, SARS-CoV-2 placentitis was associated with reduced expression of multiple apoptotic proteins (e.g., BAD, BIM, BLXL, BCL6). In conclusion, SARS-CoV-2 placentitis and CHI are associated with enhanced myeloid cell infiltration into the intervillous space, but not in the decidua and villi. The more prominently reduced apoptosis-related protein expression in SARS-CoV-2 placentitis may lead to an exaggerated immune response, causing acute placental dysfunction and fetal demise.

MeSH

Sars-Cov-2, Fetal Distress, Myeloid Cells, Decidua, Apoptosis, Severe Acute Respiratory Syndrome-Related Coronavirus, Placenta