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Abstract：
UNASSIGNED: Preeclampsia/eclampsia (PE), a critical complication during pregnancy, has been suggested to correlate with immune cell phenotypes and levels of circulating inflammatory proteins. Our study aimed to employ a two-sample mendelian randomization (MR) analysis to assess the potential causal effects of immune cell phenotypes and circulating inflammatory proteins on the onset of PE.
UNASSIGNED: We utilized summary-level data from genome-wide association studies (GWAS). This included statistics for 371 immune cell phenotypes from 3,757 individuals in the Sardinian founder population, and data on 91 circulating inflammatory proteins from 14,824 European ancestry participants. Additionally, genetic associations related to PE were extracted from the FinnGen consortium, involving 1,413 cases and 287,137 controls. We applied inverse variance weighting (IVW) and supplementary methods like MR-Egger, weighted median, and weighted mode to comprehensively assess potential causal links.
UNASSIGNED: Our analysis revealed significant causal associations of several immune cells type and inflammatory proteins with PE. Out of the immune cell phenotypes analyzed, six immune phenotypes emerged as significant risk factors (p <0.01), mainly include CD4 on activated and secreting CD4 regulatory T cells, CD28 on CD39+ CD4+ T cells, CD127- CD8+ T cell absolute cell (AC) counts, HLA DR on HLA DR+ CD8+ T cell, CD66b on CD66b++ myeloid cells, and HLA DR on dendritic cells. And ten were identified as protective factors (p <0.01). Such as CD45 on CD33br HLA DR+ CD14-, CD33+ HLA DR+ AC, CD33+ HLA DR+ CD14- AC, CD33+ HLA DR+ CD14dim AC, CD27 on CD24+ CD27+ B cell, CD20- CD38- %B cell, IgD- CD24- %B cell CD80 on plasmacytoid DC, CD25 on CD4+ T cell, and CD25 on activated & secreting CD4 regulatory T cell. Furthermore, among the inflammatory proteins studied, five showed a significant association with PE, with three offering protective effects mainly include that C-X-C motif chemokine 1, tumor necrosis factor ligand superfamily member 14, and C-C motif chemokine 19 and two exacerbating PE risk such as STAM-binding domain and Interleukin-6 (p <0.05).
UNASSIGNED: Our study highlights the pivotal roles played by diverse immune cell phenotypes and circulating inflammatory proteins in the pathophysiology of PE. These findings illuminate the underlying genetic mechanisms, emphasizing the criticality of immune regulation during pregnancy. Such insights could pave the way for novel intervention strategies in managing PE, potentially enhancing maternal and neonatal health outcomes.
UNASSIGNED: We utilized summary-level data from genome-wide association studies (GWAS). This included statistics for 371 immune cell phenotypes from 3,757 individuals in the Sardinian founder population, and data on 91 circulating inflammatory proteins from 14,824 European ancestry participants. Additionally, genetic associations related to PE were extracted from the FinnGen consortium, involving 1,413 cases and 287,137 controls. We applied inverse variance weighting (IVW) and supplementary methods like MR-Egger, weighted median, and weighted mode to comprehensively assess potential causal links.
UNASSIGNED: Our analysis revealed significant causal associations of several immune cells type and inflammatory proteins with PE. Out of the immune cell phenotypes analyzed, six immune phenotypes emerged as significant risk factors (p <0.01), mainly include CD4 on activated and secreting CD4 regulatory T cells, CD28 on CD39+ CD4+ T cells, CD127- CD8+ T cell absolute cell (AC) counts, HLA DR on HLA DR+ CD8+ T cell, CD66b on CD66b++ myeloid cells, and HLA DR on dendritic cells. And ten were identified as protective factors (p <0.01). Such as CD45 on CD33br HLA DR+ CD14-, CD33+ HLA DR+ AC, CD33+ HLA DR+ CD14- AC, CD33+ HLA DR+ CD14dim AC, CD27 on CD24+ CD27+ B cell, CD20- CD38- %B cell, IgD- CD24- %B cell CD80 on plasmacytoid DC, CD25 on CD4+ T cell, and CD25 on activated & secreting CD4 regulatory T cell. Furthermore, among the inflammatory proteins studied, five showed a significant association with PE, with three offering protective effects mainly include that C-X-C motif chemokine 1, tumor necrosis factor ligand superfamily member 14, and C-C motif chemokine 19 and two exacerbating PE risk such as STAM-binding domain and Interleukin-6 (p <0.05).
UNASSIGNED: Our study highlights the pivotal roles played by diverse immune cell phenotypes and circulating inflammatory proteins in the pathophysiology of PE. These findings illuminate the underlying genetic mechanisms, emphasizing the criticality of immune regulation during pregnancy. Such insights could pave the way for novel intervention strategies in managing PE, potentially enhancing maternal and neonatal health outcomes.
摘要：
■先兆子痫/子痫（PE），怀孕期间的严重并发症，已被认为与免疫细胞表型和循环炎症蛋白的水平相关。我们的研究旨在采用双样本孟德尔随机化（MR）分析来评估免疫细胞表型和循环炎症蛋白对PE发作的潜在因果影响。
■我们利用了来自全基因组关联研究（GWAS）的汇总水平数据。这包括撒丁岛创始人群体中3,757个人的371种免疫细胞表型的统计数据，以及来自14,824名欧洲祖先参与者的91种循环炎症蛋白的数据。此外,与PE相关的遗传关联是从FinnGen财团中提取的，涉及1,413例和287,137例控制。我们应用了方差逆加权(IVW)和MR-Egger等补充方法，加权中位数，和加权模式来全面评估潜在的因果关系。
■我们的分析揭示了几种免疫细胞类型和炎症蛋白与PE的显著因果关联。在分析的免疫细胞表型中，六种免疫表型是显著的危险因素(p<0.01)，主要包括CD4上激活和分泌的CD4调节性T细胞，CD39+CD4+T细胞上的CD28，CD127-CD8+T细胞绝对细胞（AC）计数，HLADR+CD8+T细胞,CD66b+髓系细胞上的CD66b，和树突状细胞上的HLA-DR。10个为保护因素(p<0.01)。如CD33brHLADR+CD14-上的CD45，CD33+HLADR+AC，CD33+HLADR+CD14-AC,CD33+HLADR+CD14dimAC,CD24+CD27+B细胞上的CD27，CD20-CD38-%B细胞,浆细胞样DC上的IgD-CD24-%B细胞CD80，CD4+T细胞上的CD25，和CD25在活化和分泌的CD4调节性T细胞上。此外，在研究的炎症蛋白中，五个与体育有显著关联，具有保护作用的三个主要包括C-X-C基序趋化因子1、肿瘤坏死因子配体超家族成员14和C-C基序趋化因子19，以及两个加重PE风险的STAM结合域和白细胞介素6（p<0.05）。
■我们的研究强调了不同免疫细胞表型和循环炎症蛋白在PE病理生理学中的关键作用。这些发现阐明了潜在的遗传机制，强调怀孕期间免疫调节的重要性。这些见解可以为体育管理中的新干预策略铺平道路，可能增强孕产妇和新生儿的健康结果。
■我们利用了来自全基因组关联研究（GWAS）的汇总水平数据。这包括撒丁岛创始人群体中3,757个人的371种免疫细胞表型的统计数据，以及来自14,824名欧洲祖先参与者的91种循环炎症蛋白的数据。此外,与PE相关的遗传关联是从FinnGen财团中提取的，涉及1,413例和287,137例控制。我们应用了方差逆加权(IVW)和MR-Egger等补充方法，加权中位数，和加权模式来全面评估潜在的因果关系。
■我们的分析揭示了几种免疫细胞类型和炎症蛋白与PE的显著因果关联。在分析的免疫细胞表型中，六种免疫表型是显著的危险因素(p<0.01)，主要包括CD4上激活和分泌的CD4调节性T细胞，CD39+CD4+T细胞上的CD28，CD127-CD8+T细胞绝对细胞（AC）计数，HLADR+CD8+T细胞,CD66b+髓系细胞上的CD66b，和树突状细胞上的HLA-DR。10个为保护因素(p<0.01)。如CD33brHLADR+CD14-上的CD45，CD33+HLADR+AC，CD33+HLADR+CD14-AC,CD33+HLADR+CD14dimAC,CD24+CD27+B细胞上的CD27，CD20-CD38-%B细胞,浆细胞样DC上的IgD-CD24-%B细胞CD80，CD4+T细胞上的CD25，和CD25在活化和分泌的CD4调节性T细胞上。此外，在研究的炎症蛋白中，五个与体育有显著关联，具有保护作用的三个主要包括C-X-C基序趋化因子1、肿瘤坏死因子配体超家族成员14和C-C基序趋化因子19，以及两个加重PE风险的STAM结合域和白细胞介素6（p<0.05）。
■我们的研究强调了不同免疫细胞表型和循环炎症蛋白在PE病理生理学中的关键作用。这些发现阐明了潜在的遗传机制，强调怀孕期间免疫调节的重要性。这些见解可以为体育管理中的新干预策略铺平道路，可能增强孕产妇和新生儿的健康结果。
