The causal role of circulating immunity‐inflammation in preeclampsia: A Mendelian randomization

Abstract

AbstractPatients 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.