Predictive biomarkers and maternal immune alterations in postpartum preeclampsia reveal an immune-driven pathology
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PROVIDER: PRJNA1093097 | ENA |
REPOSITORIES: ENA
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Project description:Postpartum preeclampsia (PPPE) is an under-diagnosed condition, developing within 48 hours to 6 weeks following an uncomplicated pregnancy. The etiology of PPPE is still unknown, leaving patients vulnerable and making the identification and treatment of patients requiring postpartum care an unmet need. We aimed to understand the immune contribution to PPPE at the time of diagnosis, as well as uncover the predictive potential of perinatal biomarkers for the early postnatal identification of high-risk patients. Placentas were collected at delivery from uncomplicated pregnancies (CTL) and PPPE patients for immunohistochemistry analysis. In this initial study, blood samples in PPPE patients were collected at the time of PPPE diagnosis (48h-25 days postpartum; mean 7.4 days) and compared to CTL blood samples taken 24h after delivery. Single-cell transcriptomics, flow cytometry, intracellular cytokine staining, and the circulating levels of inflammatory mediators were evaluated in the blood. Placental CD163+ cells and 1st trimester blood pressures can be valuable non-invasive and predictive biomarkers of PPPE with strong clinical application prospects. Furthermore, changes in immune cell populations, as well as cytokine production by CD14+, CD4+, and CD8+ cells, suggested a dampened response with an exhausted phenotype including decreased IL1b, IL12, and IFNg as well as elevated IL10. Understanding maternal immune changes at the time of diagnosis and prenatally within the placenta in our sizable cohort will serve as groundwork for pre-clinical and clinical research, as well as guiding clinical practice for example in the development of immune-targeted therapies, and early postnatal identification of patients who would benefit from more thorough follow-ups and risk education in the weeks following an uncomplicated pregnancy.
2024-03-28 | GSE262745 | GEO
Project description:Preeclampsia (PE) is characterized by sustained hypertension and proteinuria at a gestational age of 20 weeks or more. Immune system alterations are associated with the origin and the pathophysiology of preeclampsia, however, little is known about the landscape and heterogeneity of maternal immune system at the single-cell level. In this study, we performed single-cell RNA sequencing of 80,429 cells in PE patients and health controls, including T cells, B cells, natural killer (NK) cells, myeloid cells in peripheral blood mononuclear cells to characterize the immune cell subgroups at the pregnant and postpartum stages of PE. Our work showed that there was excessive activation of B cells, monocytes and NK cells in PE patients at the pregnant stage. Additionally, lower immune response activation was noticed in CD4+ and CD8+ T cells in PEs, especially the low-activation of memory T cells at the pregnant and postpartum stages. Moreover, there was a higher activation of B cells in pregnancy persisted postpartum in PEs, together with lower activation of memory T cells. These indicated their persistent effects on PE and its recurrence risks.
2022-11-15 | GSE192693 | GEO
Project description:Preeclampsia is a severe placenta-related pregnancy disorder that is generally divided into two subtypes named early-onset preeclampsia (onset <34 weeks of gestation), and lateonset preeclampsia (onset ≥34 weeks of gestation), with distinct pathophysiological origins. Both forms of preeclampsia have been associated with maternal systemic inflammation. However, alterations in the placental immune system have been less well characterized. Here, we studied immunological alterations in early- and late-onset preeclampsia placentas using a targeted expression profile approach. RNA was extracted from snap-frozen placenta samples (healthy n=13, early-onset preeclampsia n=13, and late-onset preeclampsia n=6). The expression of 730 immune-related genes from the Pan Cancer Immune Profiling Panel was measured, and the data were analyzed Q10 in the advanced analysis module of nSolver software (NanoString Technology). The results showed that early-onset preeclampsia placentas displayed reduced expression of complement, and toll-like receptor (TLR) associated genes, specifically TLR1 and TLR4. Mast cells and M2 macrophages were also decreased in early-onset preeclampsia compared to healthy pl acentas. The findings were confirmed by an immunohistochemistry approach using 20 healthy, 19 early-onset preeclampsia, and 10 late-onset preeclampsia placentas. We conclude that the placental innate immune system is altered in early-onset preeclampsia compared to uncomplicated pregnancies. The absence of these alterations in late-onset preeclampsia placentas indicates dissimilar immunological profiles. The study revealed distinct pathophysiological processes in earlyonset and late-onset preeclampsia placentas and imply that a tailored treatment to each subtype is desirable.
2021-12-13 | GSE190639 | GEO
Project description:Preeclampsia (PE) is a multisystem pregnancy complication constituting a major cause of maternal and fetal morbidity and mortality. Factors pointing to a placental origin are the development of the pathology only during pregnancy, and its disappearance in the post-partum period. Our study identified a specific signature of PE including five Gene Ontology clusters including "angiogenesis and differentiation", "cell cycle”, "cell adhesion", "inflammatory response" and "cellular metabolism". Interestingly, we identified DUSP1 as a biomarker of interest in PE. Pregnant women with PE have a higher concentration of DUSP1 in serum in the first trimester of pregnancy compared to healthy donors. Interesting, at a distance from childbirth DUSP1 finds a rate like the control group showing the predictive interest of DUSP1 as a predictive biomarker of PE
2024-03-26 | GSE262147 | GEO
Project description:Early-Onset Preeclampsia Is Associated With Gut Microbial Alterations in Antepartum and Postpartum Women
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Project description:Placental Immune alterations in early-onset preeclampsia and late-onset preeclampsia
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Project description:To identify early predictive biomarkers for postpartum depression using peripheral blood gene expression profiles
2013-03-29 | GSE45603 | GEO
Project description:The placenta plays an important role as a regulator of fetal nutrition and growth throughout development and placental factors contribute to gestational abnormalities such as preeclampsia. This study describes the genome-wide gene expression profiles of a large (n=60) set of human placentas in order to uncover gene expression patterns associated with preeclampsia. In addition to confirming changes in expression of soluble factors associated with preeclampsia such as sFLT1 (soluble fms-like tyrosine kinase-1), sENG (soluble endoglin), and INHA (inhibin alpha), we also find changes in immune-associated signaling pathways, offering a potential upstream explanation for the shallow trophoblast invasion and inadequate uterine remodeling typically observed in pathogenesis of preeclampsia. Notably, we also find evidence of preeclampsia-associated placental upregulation of sialic acid acetylesterase (SIAE), a gene functionally associated with autoimmune diseases. 23 preeclamptic, and 37 control placentas included in this study were collected during the years of 2004-2008 and hybridized in two batches to microarrays. Samples were randomized across arrays to control for array and batch variability.
2010-12-10 | E-GEOD-25906 | biostudies-arrayexpress
Project description:Cattle with subclinical endometritis (SCE) are sub-fertile, but there is no predictive or diagnosis tool for subclinical uterine disease. The hypothesis for this study was that endometrial inflammation is reflected in peripheral blood leucocytes gene expression. Transcriptome patterns in healthy cows and in cows with SCE at 45-55 days postpartum were evaluated using circulating white blood cells and endometrial biopsies samples collected from the same animals. Bioinformatics analyses of microarray-based transcriptional data identified gene profiles associated with distinct biological functions in circulating white blood cells and endometrium. In circulating white blood cells SCE promote a pro-inflammatory environment related to the activation of inflammation, whereas in the endometrium functions also related to tissue remodeling. Nineteen differentially expressed genes were altered both in circulating white blood cells and in the endometrium of SCE cows compared with healthy cows. Among these genes, transcript abundance of immune factors C3, C2, LTF, PF4 and TRAPPC13 were up-regulated in SCE cows at 45-55 days postpartum. Moreover, the mRNA expression of C3, CXCL8, LTF, TLR2 and TRAPPC13 was temporally regulated during the postpartum period in circulating white blood cells from healthy cows compared with SCE cows. This observation might indicate an advantageous activation of the immune system in healthy animals. The transcript abundance of these genes might also be used as an indicator for subsequent postpartum uterine health.
2019-08-20 | GSE115667 | GEO
Project description:Dual specificity phosphate 1 (DUSP1) has a key non-invasive predictive marker in preeclampsia
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