Late first trimester circulating microparticle proteins predict the risk of preeclampsia < 35 weeks and suggest phenotypic differences among affected cases

Abstract

We hypothesize that first trimester circulating micro particle (CMP) proteins will define preeclampsia risk while identifying clusters of disease subtypes among cases. We performed a nested case–control analysis among women with and without preeclampsia. Cases diagnosed &lt; 34 weeks’ gestation were matched to controls. Plasma CMPs were isolated via size exclusion chromatography and analyzed using global proteome profiling based on HRAM mass spectrometry. Logistic models then determined feature selection with best performing models determined by cross-validation. K-means clustering examined cases for phenotypic subtypes and biological pathway enrichment was examined. Our results indicated that the proteins distinguishing cases from controls were enriched in biological pathways involved in blood coagulation, hemostasis and tissue repair. A panel consisting of C1RL, GP1BA, VTNC, and ZA2G demonstrated the best distinguishing performance (AUC of 0.79). Among the cases of preeclampsia, two phenotypic sub clusters distinguished cases; one enriched for platelet degranulation and blood coagulation pathways and the other for complement and immune response-associated pathways (corrected p &lt; 0.001). Significantly, the second of the two clusters demonstrated lower gestational age at delivery (p = 0.049), increased protein excretion (p = 0.01), more extreme laboratory derangement (p &lt; 0.0001) and marginally increased diastolic pressure (p = 0.09). We conclude that CMP-associated proteins at 12 weeks’ gestation predict the overall risk of developing early preeclampsia and indicate distinct subtypes of pathophysiology and clinical morbidity.

Preeclamptic Women Have Disrupted Placental microRNA Expression at the Time of Preeclampsia Diagnosis: Meta-Analysis

“…PE is a multi-factorial, multisystemic pregnancy specific condition found typically after 20 weeks of gestation or early post-delivery (American College of Obstetricians and Gynecologists, 2019). Although clinical symptoms appear relatively late in pregnancy, PE pathology begins early, making the identification of potential biomarkers during the first trimester a possible strategy for identifying predictors of PE (McElrath et al, 2020). Several potential biomarkers already have been evaluated: C reactive protein (CRP), cytokines (IL-6, IL-8, TNF-α), microparticle proteins (C1RL, GP1BA, VTNC, and ZA2G), oxidative stress markers (malondialdehyde -MDA), and genetic factors (PAI-1 4G/5G polymorphism) (Black and Horowitz, 2018;Giannakou et al, 2018;Taravati and Tohidi, 2018;McElrath et al, 2020).…”

Biomarkers in Prediction of Preeclampsia

“…The molecular signatures of trophoblastic microparticles might also additionally offer crucial information about the condition of the placenta while non-placental microparticles, including exosomes, might also additionally mirror maternal health or disease state. In line with those findings, latest research identified potential biomarkers of preeclampsia with the examining the changes in the type, amount, and content material of these exosomes [79][80][81][82].…”

N6-Methyladenosine Methylomic Landscape of Lung Tissues in Murine Acute Allergic Asthma

“…For example, FCER2A (CD23) is associated with the activation of B cells ( 67 ). GP1BA , a glycoprotein component on the surface of platelets is often related to clotting function ( 68 ) and has also been considered to participate in lung inflammation ( 69 , 70 ). IL-7 is considered to activate eosinophils and has a pivotal function in allergic inflammation in asthma ( 71 ), but is also essential for T- and B-cell development ( 72 ).…”