Reduced Placental CD24 in Preterm Preeclampsia Is an Indicator for a Failure of Immune Tolerance

Abstract

Introduction: CD24 is a mucin-like glycoprotein expressed at the surface of hematopoietic and tumor cells and was recently shown to be expressed in the first trimester placenta. As it was postulated as an immune suppressor, CD24 may contribute to maternal immune tolerance to the growing fetus. Preeclampsia (PE), a major pregnancy complication, is linked to reduced immune tolerance. Here, we explored the expression of CD24 in PE placenta in preterm and term cases. Methods: Placentas were derived from first and early second trimester social terminations (N = 43), and third trimester normal term delivery (N = 67), preterm PE (N = 18), and preterm delivery (PTD) (N = 6). CD24 expression was determined by quantitative polymerase chain reaction (qPCR) and Western blotting. A smaller cohort included 3–5 subjects each of term and early PE, and term and preterm delivery controls analyzed by immunohistochemistry. Results: A higher expression (2.27-fold) of CD24 mRNA was determined in the normal term delivery compared to first and early second trimester cases. The mRNA of preterm PE cases was only higher by 1.31-fold compared to first and early second trimester, while in the age-matched PTD group had a fold increase of 5.72, four times higher compared to preterm PE. The delta cycle threshold (ΔCt) of CD24 mRNA expression in the preterm PE group was inversely correlated with gestational age (r = 0.737) and fetal size (r = 0.623), while correlation of any other group with these parameters was negligible. Western blot analysis revealed that the presence of CD24 protein in placental lysate of preterm PE was significantly reduced compared to term delivery controls (p = 0.026). In immunohistochemistry, there was a reduction of CD24 staining in villous trophoblast in preterm PE cases compared to gestational age-matched PTD cases (p = 0.042). Staining of PE cases at term was approximately twice higher compared to preterm PE cases (p = 0.025) but not different from normal term delivery controls. Conclusion: While higher CD24 mRNA expression levels were determined for normal term delivery compared to earlier pregnancy stages, this expression level was found to be lower in preterm PE cases, and could be said to be linked to reduced immune tolerance in preeclampsia.

Modeling Preeclampsia In Vitro: Polymorphic Variants of STOX1-A/B Genes Can Downregulate CD24 in Trophoblast Cell Lines

“…As was previously reported [27,28], it was also found that the protein is co-expressed with Siglec-10, mainly in the close vicinity of the invasive extravillous trophoblasts [34]. In another study, we used qRT-PCR analysis to show a significant increase in CD24 expression from the first and early second trimester to the third trimester and term delivery [35]. In contrast to the normal course of pregnancy, in cases of early (before 34 weeks gestation), and preterm (before 37 weeks gestation) preeclampsia, the level of CD24 mRNA is reduced [35] compared to cases of term delivery and preterm delivery (before 37 weeks gestation).…”

Spatiotemporal coordination at the maternal-fetal interface promotes trophoblast invasion and vascular remodeling in the first half of human pregnancy

“…S6o, Supplementary Table 7). Interestingly, reduced global placental CD24 expression has been associated with an increased risk of developing preterm preeclampsia, yet EVT-specific expression of CD24 transcripts has not yet been reported 65, 72 . Given that abnormal decidual and spiral artery remodeling are thought to play a major role in preeclampsia 73 , we sought to determine if other genes involved in EVT invasion and vascular remodeling had previously been implicated as well.…”

Knowledge, attitude and practice of women towards preeclampsia in port blair

“…Hence, the knowledge attitude and practices are not beneficial for increasing their concern about this dangerous disease. Apart from that, the attitude also shows that they need a proper awareness program in this context for proceeding with the best result (Sammar et al 2021). Not only that, it can be seen that preeclampsia affected arteries that carry blood flow to the placenta.…”