Maternal cytokine and cellular adhesion molecules profile in pregnant women with and without congenital heart disease.

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine Pub Date : 2025-02-10 DOI:10.1016/j.cyto.2025.156886

Francois Dos Santos, Philip J. Steer, Mark R. Johnson

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引用次数: 0

Abstract

Introduction

Despite corrective surgery, patients with congenital heart disease (CHD) have residual regions of disturbed oscillatory blood flow which can induce upregulation of proinflammatory cytokines and adhesion molecules. Data on cytokine and cellular adhesion molecule (CAM) profiles in low risk pregnancy and pregnancy complicated by CHD are limited. The objective of this work was to study the profile of IL-6, IL-10, TNFα, ghrelin, GROα, and ICAM/VCAM in pregnancy in women with and without CHD and test the hypothesis that the circulating levels of these are correlated with obstetric outcomes.

Methods

Prospective study of women ≥18 years carrying a singleton low risk pregnancy low-risk (LR-group) and pregnant women with CHD (CHD-group). Study visits were conducted between 10 and 14, 18–22 and 30–34 weeks' gestation with blood sampling for immune profiling using the Bio-Plex® Multiplex Immunoassay. The immune profile was investigated in both groups and correlated with obstetric outcomes. This study was approved by the Health Research Authority and the London South East Research Ethics Committee (REC reference: 17/LO/0970).

Results

Forty-five samples in 30 participants with CHD and 45 gestational age-matched samples from 34 low-risk pregnant women were analysed. Women in the CHD-group delivered earlier (38 + 6 weeks vs 39 + 4 weeks, p = 0.005) and had smaller babies (2940 g, 30.0 centile vs 3415 g, 63.5 centile, p < 0.001). There were no significant differences in the levels of IL-6, IL-10 or TNFαin both groups across trimesters. Levels of GROα increased in both groups but less so in the CHD group. Levels of ghrelin decreased in both groups but less so in the CHD group. Levels of ICAM decreased as pregnancy progressed in the CHD group. Levels of VCAM increased in both groups but more significantly in the CHD-group (second trimester, p < 0.001; third trimester, p = 0.045). Women in the CHD-group had higher levels if IL-6 (p = 0.005) and ICAM (p < 0.001) lower levels of IL-10 in the third trimester (p = 0.018). There was a significant positive association between levels of IL-6 in the first trimester and birthweight centiles (r_s = 1.00, p < 0.001) in the CHD group.

Conclusion

There was minimal fluctuation in the levels of the studies cytokines during pregnancy with exception of GROα and ghrelin, both implicated in fetal growth. Women with CHD had higher levels of proinflammatory cytokines and ICAM in the first trimester, and lower levels of IL-10 in the third trimester, suggesting a more proinflammatory state. High levels of VCAM in the CHD group could be secondary to endothelial activation.

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有和无先天性心脏病孕妇的母体细胞因子和细胞粘附分子谱

尽管进行了矫正手术，先天性心脏病（CHD）患者仍存在振荡血流紊乱的残余区域，可诱导促炎细胞因子和粘附分子的上调。低危妊娠和合并冠心病妊娠的细胞因子和细胞粘附分子（CAM）谱资料有限。这项工作的目的是研究IL-6、IL-10、TNFα、ghrelin、GROα和ICAM/VCAM在有和无冠心病妇女妊娠期的分布，并检验这些循环水平与产科结局相关的假设。方法前瞻性研究≥18岁单胎低危妊娠低危组（lr组）和合并冠心病孕妇（冠心病组）。研究人员在妊娠10至14周、18-22周和30-34周期间进行了研究访问，并使用Bio-Plex®多重免疫分析法进行了血液取样，以进行免疫分析。对两组的免疫状况进行了调查，并与产科结局相关。这项研究得到了卫生研究管理局和伦敦东南研究伦理委员会的批准（REC参考：17/LO/0970）。结果分析了30例冠心病患者的45个样本和34例低危孕妇的45个胎龄匹配样本。冠心病组妇女分娩较早（38 + 6周vs 39 + 4周，p = 0.005），婴儿较小(2940 g， 30.0百分位vs 3415 g， 63.5百分位，p <；0.001)。两组妊娠期间IL-6、IL-10、tnf - α水平均无显著差异。两组的GROα水平均升高，但冠心病组的GROα水平较低。两组的胃饥饿素水平均有所下降，但冠心病组的下降幅度较小。在冠心病组，ICAM水平随着妊娠进展而下降。VCAM水平在两组均升高，但在冠心病组(妊娠中期，p <；0.001;妊娠晚期，p = 0.045)。冠心病组女性IL-6 （p = 0.005）和ICAM (p <；0.001)妊娠晚期IL-10水平降低（p = 0.018）。妊娠早期IL-6水平与出生体重百分位数之间存在显著正相关(rs = 1.00, p <；0.001)。结论妊娠期间，除GROα和ghrelin外，其他细胞因子的水平波动很小，这两种细胞因子都与胎儿生长有关。CHD女性在妊娠早期有较高水平的促炎细胞因子和ICAM，在妊娠晚期有较低水平的IL-10，提示有较强的促炎状态。冠心病组高水平的VCAM可能继发于内皮细胞活化。

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来源期刊

Cytokine 医学-免疫学

CiteScore

7.60

自引率

2.60%

发文量

262

审稿时长

48 days

期刊介绍： The journal Cytokine has an open access mirror journal Cytokine: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. * Devoted exclusively to the study of the molecular biology, genetics, biochemistry, immunology, genome-wide association studies, pathobiology, diagnostic and clinical applications of all known interleukins, hematopoietic factors, growth factors, cytotoxins, interferons, new cytokines, and chemokines, Cytokine provides comprehensive coverage of cytokines and their mechanisms of actions, 12 times a year by publishing original high quality refereed scientific papers from prominent investigators in both the academic and industrial sectors. We will publish 3 major types of manuscripts: 1) Original manuscripts describing research results. 2) Basic and clinical reviews describing cytokine actions and regulation. 3) Short commentaries/perspectives on recently published aspects of cytokines, pathogenesis and clinical results.