Analysis of changes in high-mobility group box 1, receptor for advanced glycation endproducts, and T helper 17/regulatory T balance in severe preeclampsia with acute heart failure

Abstract

We measured the levels of High-Mobility Group Box 1 (HMGB1), Receptor for Advanced Glycation Endproducts (RAGE), T Helper 17 cells (Th17), Regulatory T cells (Treg), and related cytokines in the peripheral blood of patients with severe preeclampsia (SPE) complicated with acute heart failure (AHF) to explore the expression changes in these indicators. In total, 96 patients with SPE admitted to Gansu Provincial Maternity and Child-care Hospital between June 2020 and June 2022 were included in the study. The patients were divided into SPE+AHF (40 patients) and SPE (56 patients) groups based on whether they suffered from AHF. Additionally, 56 healthy pregnant women who either received prenatal examinations or were admitted to our hospital for delivery during the same period were selected as the healthy control group. An enzyme-linked immunosorbent assay was performed to detect the expression levels of HMGB1, RAGE, interleukin (IL)-17, IL-6, transforming growth factor β (TGF-β), IL-10, and NT-proBNP in plasma. Flow cytometry was employed to determine the percentages of Th17 and Treg cells. Compared to the healthy control group, the SPE+AHF and SPE groups had higher plasma levels of HMGB1 and RAGE expression, higher Th17 percentage and Th17/Treg ratio, and lower Treg percentage. Compared to the SPE group, the SPE+AHF group had higher plasma levels of HMGB1 and RAGE expression, higher Th17 percentage and Th17/Treg ratio, and lower Treg percentage (P < .05). In patients with SPE with AHF, plasma HMGB1 was positively correlated with RAGE, Th17, Th17/Treg, IL-17, and IL-6 and was negatively correlated with TGF-β and IL-10 (P < .05). Our findings revealed that patients with SPE with AHF had elevated levels of HMGB1 and RAGE while exhibiting Th17/Treg immune imbalance, suggesting that the abnormal expression of these indicators may be involved in the pathogenesis of SPE with AHF.

Keywords: Th17/Treg; acute heart failure; high‐mobility group box 1 protein; receptor for advanced glycation endproducts; severe preeclampsia.

FIGURE 1

Flow cytometry results of Treg and Th17 in peripheral blood. Note: A and F are the results of PMA/Ionomycin unstimulated staining of IL‐17A (Th17 cells) and rat IgG2a isotype control (Treg cells), respectively. B and G are the Th17 and Treg detection results, respectively, of the healthy control group. C and H are the Th17 and Treg detection results, respectively, of the SPE group. D and I are the Th17 and Treg detection results, respectively, of the SPE+AHF group. E and J are the comparisons of the Th17 and Treg detection results, respectively, among the different groups, vs. healthy control group, a P < .05; vs. SPE group, b P < .05. SPE: severe preeclampsia; AHF: acute heart failure; Th17: T helper 17 cells; Treg: regulatory T cells.

FIGURE 2

Critical results of random forest analysis characteristics of factors predicting AHF in patients with SPE. Note: HMGB1: high mobility group box 1 protein; RAGE: receptor for advanced glycation end products; Th17: T helper 17 cells; Treg: regulatory T cells; IL‐17: interleukin 17; IL‐6: interleukin 6; TGF‐β: transforming growth factor β; IL‐10: interleukin 10.

FIGURE 3

ROC curve of each index in the diagnosis of AHF in SPE patients. Note: HMGB1: high mobility group box 1 protein; RAGE: receptor for advanced glycation end products; Th17: T helper 17 cells; Treg: regulatory T cells; IL‐17: interleukin 17; IL‐6: interleukin 6; TGF‐β: transforming growth factor β; IL‐10: interleukin 10.