Complement System and Neutrophil Extracellular Traps Define a Shared Immune Signature in Early- and Late-Onset Preeclampsia

Background: Preeclampsia (PE) is a leading cause of maternal and perinatal morbidity worldwide, yet its mechanisms remain poorly understood. Dysregulated innate im-munity, specifically aberrant complement activation and excessive neutrophil extracel-lular traps (NETs) formation, contributes to endothelial dysfunction and inflammation in preeclampsia. However, the interaction between complement activation and NETs, as well as the differences between these immune pathways in early-onset and late-onset preeclampsia, remain unclear. To address this gap, we assessed complement components and NET markers across various preeclampsia phenotypes and examined their rela-tionships. Methods: Plasma samples were collected from 56 women with early-onset preeclampsia (EO-PE) before 34 weeks, 32 with late-onset preeclampsia (LO-PE) after 34 weeks, and 32 healthy pregnant women in the control group. Complement components (C1q, C3, C3a, C4, and the terminal complement complex, TCC) and NETs markers (MPO-DNA, cit-rullinated histone H3, and cathepsin G) were measured using ELISA. Group differences were assessed with non-parametric tests, and associations between markers and clinical variables were analyzed using Spearman correlations. Results: We observed higher levels of C1q, C3, C3a, and TCC in pregnant women with severe preeclampsia compared with healthy pregnancies (p < 0.001), while C4 levels remained unchanged. Among neutrophil trap biomarkers, MPO-DNA levels were el-evated in EO-PE (p = 0.019), while CitH3 and cathepsin G levels did not differ significantly between groups. Strong correlations were observed between MPO-DNA and TCC (ρ = 0.30, p = 0.013), as well as between cathepsin G and C3a (ρ = 0.40, p = 0.0007), indicating NETs–complement interactions. Patterns of complement and NETs activation were similar in early and late preeclampsia, despite differences in gestational age. Conclusions: The observed associations between MPO-DNA and TCC, and between cathepsin G and C3a, indicate meaningful crosstalk between NETs and complement ac-tivation. These findings support the role of innate immune dysregulation in preeclampsia and highlight NETs–complement interactions as potential targets for diagnostic and therapeutic approaches.