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

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.

CD24 is a Potential Biomarker for Prognosis in Human Breast Carcinoma

Background/Aims: CD24 is a highly glycosylated mucin-like antigen on the cell surface, which has recently emerged as a novel oncogene and metastasis promoter. We performed bioinformatics analysis to investigate whether CD24 can serve as a prognostic indicator in breast cancer. Methods: CD24 expression was assessed using SAGE Genie tools and Oncomine analysis. The PrognoScan database, Kaplan-Meier Plotter, and bc-GenExMiner were used to identify the prognostic roles of CD24 in breast cancer. Results: We found that CD24 was more frequently overexpressed in breast cancer than in normal breast tissue and correlated with worse prognosis. Meanwhile, high CD24 expression was associated with increased risk of HER2, basal-like, triple-negative breast cancer, and higher Scarff-Bloom-Richardson grade. Data mining in multiple big databases confirmed a positive correlation between CD24 mRNA expression and SDC1 mRNA expression in breast cancer tissue. Conclusions: Our findings suggest that CD24 overexpression is more common in breast cancer than in corresponding normal tissue. In addition, CD24 and SDC1 can serve as prognostic indicators for breast cancer. However, large-scale and comprehensive research is needed to further confirm these results.

Human T lymphocytes and hematopoietic cell lines express CD24- associated carbohydrate epitopes in the absence of CD24 mRNA or protein

The CD24 surface antigen is a small glycophosphatidylinositol (GPI)-anchored glycoprotein found on human granulocytes and most B lymphocytes. Many CD24 monoclonal antibodies (MoAbs) have been described that identify several epitopes, with the majority of them related to carbohydrate structures associated with the CD24 molecule. Considerable variation has been observed in the apparent tissue distribution of the CD24 antigen depending on the MoAb used, and hence the CD24 epitope studied. In this study, CD24 expression by human cell lines and normal hematopoietic call populations was assessed using a panel of carbohydrate and protein core-specific CD24 MoAbs and reverse transcriptase polymerase chain reaction (RT-PCR) analysis. A number of CD24 carbohydrate epitope-reactive MoAbs bound to both T lymphocytes and several hematopoietic cell lines, despite the absence of concomitant CD24 mRNA or detectable surface CD24 core protein in the same cells. This additional CD24 MoAb reactivity on T lymphocytes was, in common with that observed on granulocytes (CD24 protein+), specifically inhibited by the presence of both sialyllactose and mucin. Similarly, the binding of carbohydrate epitops-reactive CD24 MoAb was reduced on both T lymphocytes and granulocytes by pretreatment with phospholipase C, pronase, or neuraminidase. Together, the data indicate that a number of CD24-associated carbohydrate epitopes have a broader tissue distribution than the CD24 protein and are expressed on additional GPI-linked molecule(s). These findings have immediate implications for both leukemia phenotyping and attempts to examine CD24 function with CD24 MoAb.