Dataset Information

Identification of potential protein biomarkers associated with congenital diaphragmatic hernia in human amniotic fluid

ABSTRACT: Congenital diaphragmatic hernia (CDH) results from incomplete diaphragm development and can be associated with pulmonary hypoplasia, pulmonary hypertension, and heart failure. Currently, few biomarkers are available. Since amniotic fluid comprises proteins of both fetal and maternal origin, its analysis could provide insights on mechanisms underlying CDH and provide biomarkers for early diagnosis, severity of pulmonary changes and response to treatment. The study objective was to identify proteomic changes in amniotic fluid consistently associated with CDH. Amniotic fluid was obtained at term (37-39 weeks) from women with normal pregnancies (n=5) or carrying fetuses with CDH (n=5). After immuno-depletion of the highest abundance proteins, off-line fractionation and high-resolution tandem mass spectrometry were performed and quantitative differences between the proteomes of the groups were determined. Of 1036 proteins identified, 218 were differentially abundant. Bioinformatics analysis showed significant changes in GP6 signaling, MSP-RON signaling in macrophages pathways and networks associated with cardiovascular system development and function, connective tissue disorders and dermatological conditions. Pulmonary surfactant protein B, osteopontin, kallikrein 5 and galectin 3 were investigated orthogonally using ELISA in larger cohorts to test the observed differences and showed statistically significant differences aiding in the prediction of CDH. The findings provide potential tools for improved clinical detection and management of CDH.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Amniotic Fluid

SUBMITTER: Sumit Bhutada

LAB HEAD: Suneel S. Apte

PROVIDER: PXD041165 | Pride | 2023-10-24

REPOSITORIES: Pride

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Identification of protein biomarkers associated with congenital diaphragmatic hernia in human amniotic fluid.

Bhutada Sumit S Tran-Lundmark Karin K Kramer Benjamin B Conner Peter P Lowry Ashley M AM Blackstone Eugene E Frenckner Bjorn B Mesas-Burgos Carmen C Apte Suneel S SS

Scientific reports 20230919 1

Congenital diaphragmatic hernia (CDH) is a severe birth defect frequently associated with pulmonary hypoplasia, pulmonary hypertension, and heart failure. Since amniotic fluid comprises proteins of both fetal and maternal origin, its analysis could provide insights on mechanisms underlying CDH and provide biomarkers for early diagnosis, severity of pulmonary changes and treatment response. The study objective was to identify proteomic changes in amniotic fluid consistently associated with CDH. A ...[more]

PMID: 37726509

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Project description:Intra-amniotic infection, the invasion of microbes into the amniotic cavity resulting in an inflammatory process, is a clinical condition that can lead to adverse pregnancy outcomes for the mother and fetus as well as severe long-term neonatal morbidities. Despite much research focused on the consequences of intra-amniotic infection, there is still little knowledge about the functional roles of innate immune cells that respond to invading microbes. In the current study, we performed RNA sequencing of sorted neutrophils and monocytes/macrophages from amniotic fluid from women with intra-amniotic infection to determine the transcriptomic differences between these innate immune cells. Further, we sought to identify specific transcriptomic pathways that were significantly altered by the maternal or fetal origin of amniotic fluid neutrophils and monocytes, the presence of a severe fetal inflammatory response, and pregnancy outcome (i.e. preterm or term delivery). We showed that significant transcriptomic differences exist between amniotic fluid neutrophils and monocytes/macrophages from women with intra-amniotic infection that are indicative of the distinct roles these cells play. We also found that amniotic fluid monocytes/macrophages of fetal origin display impaired ability to clear out microbes invading the amniotic cavity compared to those of maternal origin. Notably, we demonstrate that the transcriptomic changes in amniotic fluid monocytes/macrophages are heavily associated with the severity of the fetal inflammatory response, suggesting that the trafficking of fetal neutrophils throughout the umbilical cord is partially modulated by monocytes/macrophages in the amniotic cavity. Finally, we show that amniotic fluid neutrophils and monocytes/macrophages from preterm deliveries display enhanced transcriptomic activity compared to those from term deliveries, highlighting the protective role of these innate immune cells in this vulnerable period. Collectively, these findings demonstrate the underlying complexity of local innate immune responses in women with intra-amniotic infection, and provide new insights into the functions of amniotic fluid neutrophils and monocytes in the amniotic cavity.

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