Broekhuizen Michelle, van der Hoorn Marie-Louise, Vadgama Disha, Eikmans Michael, Neecke Bojou J, Duvekot Johannes J, Fraaij Pieter, Reiss Irwin K M, Mustafa Dana A M, van der Meeren Lotte E, Schoenmakers Sam
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.
Eur J Immunol. 2025 Jan;55(1):e202451386. doi: 10.1002/eji.202451386.
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.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染胎盘可导致胎儿窘迫和死亡，其特征为严重的滋养层坏死、慢性组织细胞绒毛间炎（CHI）和大量绒毛周围纤维蛋白沉积。我们旨在揭示与CHI胎盘和正常妊娠相比，SARS-CoV-2胎盘炎中与免疫相关的蛋白质的空间变化，以深入了解潜在的病理生理机制。回顾性收集了因SARS-CoV-2胎盘炎导致胎儿窘迫/死亡的病例（n = 9）、CHI病例（n = 9）和足月正常对照病例（n = 9）的胎盘。使用GeoMx数字空间分析器在三个不同区域定量53种免疫相关蛋白的表达：绒毛（胎儿区域）、绒毛间隙和蜕膜（两个母体区域）。与对照组相比，SARS-CoV-2胎盘炎和CHI仅在绒毛间隙显示出差异表达的蛋白质，包括髓系标志物（如CD40、CD11c、CD68、CD163）的上调。具体而言，SARS-CoV-2胎盘炎与多种凋亡蛋白（如BAD、BIM、BLXL、BCL6）的表达降低有关。总之，SARS-CoV-2胎盘炎和CHI与髓系细胞向绒毛间隙的浸润增强有关，但在蜕膜和绒毛中无此现象。SARS-CoV-2胎盘炎中凋亡相关蛋白表达更显著降低可能导致过度的免疫反应，引起急性胎盘功能障碍和胎儿死亡。
