Patients with systemic autoimmune diseases, such as systemic lupus erythematosus, were at a higher risk for preeclampsia. The causal relationship between immunological inflammation and preeclampsia (PE) remains uncertain. We aimed to investigate the causal relationship between circulating immune inflammation and PE. Genetically predicted blood immune cells and circulating inflammatory proteins were identified using two genome‐wide association studies (GWAS). We used a two‐sample Mendelian randomization (MR) method to determine whether circulating immunological inflammation causes PE. Our findings indicated that ten immunophenotypes were identified to be significantly associated with PE risk: CD62L‐ Dendritic Cell Absolute Count, CD86+ myeloid Dendritic Cell %Dendritic Cell, CD62L‐ myeloid Dendritic Cell Absolute Count, CD86+ myeloid Dendritic Cell Absolute Count, CD62L‐ myeloid Dendritic Cell %Dendritic Cell, CD62L‐ CD86+ myeloid Dendritic Cell %Dendritic Cell, CD62L‐ CD86+ myeloid Dendritic Cell Absolute Count, CD16 on CD14+ CD16+ monocyte, HLA DR+ Natural Killer Absolute Count, and T cell Absolute Count. Ninety‐one inflammation‐related proteins had no statistically significant effect on PE following false discovery rate (FDR) correction. Certain proteins exhibited unadjusted low p‐values that merited mention. These proteins include interleukin‐10 (OR = 0.76, 95%CI = 0.63–0.93, p = .006), fibroblast growth factor 21 (OR = 1.23, 95%CI = 1.01–1.47, p = .035), and Caspase 8 (OR = 0.65, 95%CI = 0.50–0.85, p = .001). The ELISA analysis demonstrated elevated levels of FGF‐21 and decreased levels of IL‐10 and Caspase‐8 in the plasma of patients with PE. These findings reveal that immunophenotypes and circulating inflammatory proteins may induce PE, confirming the importance of peripheral Immunity‐Inflammation in PE. The discovery has the potential to lead to earlier detection and more effective treatment techniques.

中文翻译：

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循环免疫炎症在先兆子痫中的因果作用：孟德尔随机化

患有系统性自身免疫性疾病（例如系统性红斑狼疮）的患者患先兆子痫的风险较高。免疫炎症与先兆子痫（PE）之间的因果关系仍不确定。我们的目的是研究循环免疫炎症与 PE 之间的因果关系。使用两项全基因组关联研究（GWAS）鉴定了基因预测的血液免疫细胞和循环炎症蛋白。我们使用双样本孟德尔随机化 (MR) 方法来确定循环免疫炎症是否会导致 PE。我们的研究结果表明，十种免疫表型被确定与 PE 风险显着相关：CD62L- 树突状细胞绝对计数、CD86+ 髓样树突状细胞百分比树突状细胞、CD62L- 髓样树突状细胞绝对计数、CD86+ 髓样树突状细胞绝对计数、CD62L- 髓样树突状细胞细胞树突细胞百分比、CD62L-CD86+ 骨髓树突细胞百分比、CD62L-CD86+ 骨髓树突细胞绝对计数、CD14+ CD16+ 单核细胞上的 CD16、HLA DR+ 自然杀伤细胞绝对计数和 T 细胞绝对计数。错误发现率 (FDR) 校正后，91 种炎症相关蛋白对 PE 没有统计学上的显着影响。某些蛋白质表现出未经调整的低水平p‐值得一提的价值观。这些蛋白质包括白细胞介素-10（OR = 0.76，95%CI = 0.63–0.93，p= .006)，成纤维细胞生长因子 21（OR = 1.23，95%CI = 1.01–1.47，p= .035) 和 Caspase 8 (OR = 0.65, 95%CI = 0.50–0.85,p= .001)。ELISA 分析表明，PE 患者血浆中 FGF-21 水平升高，IL-10 和 Caspase-8 水平降低。这些发现表明，免疫表型和循环炎症蛋白可能诱发肺栓塞，证实了外周免疫炎症在肺栓塞中的重要性。这一发现有可能带来更早的检测和更有效的治疗技术。