The Intensity of BCL2A1 Expression Increases According to the Stage Progression of Acute Histologic Chorioamnionitis in the Extra-Placental Membranes of Spontaneous Preterm Birth

Abstract

Our prior findings showed that BCL2A1 in neutrophils is highly expressed in the extra-placental membranes (EPMs) of both the human spontaneous preterm-birth (PTB) (i.e., PTL or preterm PROM) and nonhuman-primate PTB model. However, no data exist on whether the intensity of BCL2A1 expression quantitatively increases according to the stage progression of acute histologic chorioamnionitis (acute HCA) in EPM. The objective is to investigate whether the intensity of BCL2A1 expression quantitatively increases according to the stage progression of acute HCA in EPM among spontaneous PTB cases, as measured using QuPath. The study population included 121 singleton PTBs (gestational age [GA] at delivery < 34 weeks) due to either preterm labor or preterm PROM. With digital image analysis, we calculated the percentage of BCL2A1-positive cells in immunohistochemistry according to the stage progression of acute HCA in EPMs as the primary outcome and examined the relationship between the percentage of BCL2A1-positive cells and either the GA at delivery or the amniotic-fluid (AF) WBC count as the secondary outcome. The median percentage of BCL2A1-positive cells progressively increases with the stage progression of acute HCA in EPM (group-1 vs. group-2 vs. group-3 vs. group-4 vs. group-5; 7.62 vs. 5.15 vs. 43.57 vs. 71.07; γ = 0.552, p < 0.000001). The percentage of BCL2A1-positive cells in EPMs and the AFWBC count shows a positive correlation (γ = 0.492, p = 0.000385). Moreover, the percentage of BCL2A1-positive cells in EPMs continuously decreased with increasing GA at delivery (γ = −0.253, p = 0.005148). In conclusion, the intensity of BCL2A1 expression increases according to the stage progression of acute HCA in EPMs and the elevation of AFWBC among spontaneous PTB cases. This finding suggests BCL2A1 in EPMs may be a promising marker and target for acute HCA.