Hofbauer cell alterations and potential role in the pathophysiology of HELLP syndrome

HELLP syndrome, a severe pregnancy complication characterized by hemolysis, elevated liver enzymes, and low platelet count, is a subtype of preeclampsia (PE). However, its rapid onset and unique clinical features suggest distinct underlying mechanisms. Although Hofbauer cells are essential for maintaining immune homeostasis, their involvement in HELLP syndrome remains unclear. We conducted transcriptomic analysis of public data sets to assess macrophage-associated gene expression in placentas from control, PE, and HELLP cases. Immunohistochemistry and image analysis were performed on formalin-fixed paraffin-embedded placental tissues to quantify macrophage density and size, and electron microscopy was conducted to evaluate ultrastructural features. Gene expression analysis revealed a significant reduction in AIF1 (Iba1) and CD163 expression in PE placentas, while CD163 expression was relatively preserved in HELLP. Immunohistochemistry confirmed decreased Hofbauer cell density in PE placentas, whereas enlarged Hofbauer cells with increased rough endoplasmic reticulum, suggesting enhanced activation status, were seen in HELLP. Hofbauer cells exhibit distinct morphological and molecular changes in HELLP syndrome compared with PE, which implicates their potential involvement in the pathophysiology of HELLP. These findings provide new insights into the fetal immune environment in pregnancy-related hypertensive disorders.