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Pathway analysis of miRNA revealing immunologic alteration in lymphocyte immune response and T cell differentiation in Fontan patients with protein-losing enteropathy

ABSTRACT: Pathway analysis of miRNA revealing immunologic alteration in lymphocyte immune response and T cell differentiation in Fontan patients with protein-losing enteropathy

PROVIDER: PRJNA540866 | ENA |

REPOSITORIES: ENA

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Pathway analysis of miRNA revealing immunologic alteration in lymphocyte immune response and T cell differentiation in Fontan patients with protein-losing enteropathy

Project description:Protein losing enteropathy (PLE) is a severe complication of Fontan circulation with increased morbidity and mortality. The underlying pathophysiologic mechanism leading to the development of PLE in Fontan patients remain largely unknown. We performed microarray-based microRNA (miRNA) expression profiling from whole blood to generate hypotheses about relevant pathways involved in PLE pathogenesis controlled by miRNA signature.

2020-05-01 | GSE130647 | GEO

CD55 Deficiency, Early-Onset Protein-Losing Enteropathy and Thrombosis

Project description:CD55 Deficiency, Early-Onset Protein-Losing Enteropathy and Thrombosis

| PRJNA389487 | ENA

Comparative analysis of miRNA profile in sheep serum and serum-derived extracellular vesicles before and after single stage Fontan surgery

Project description:There are no curative treatment options for patients with single ventricle disease. Rather, the standard of care includes a series of palliative procedures that culminate in the Fontan operation, which, while life-saving, nevertheless reduces longevity and quality of life. The cause of late term death in these patients is typically ascribed to insidious end organ sequelae associated with the Fontan circulation. The etiology underlying these pathological processes remains unknown, but is thought to be diverse and multifactorial, arising from progressive deterioration of end-organ function due to the non-physiologic Fontan hemodynamics and its consequences on tissue perfusion and remodeling.Our overall goal is to evaluate the impact of Fontan physiology on cardiopulmonary remodeling over long periods in an ovine Fontan survival model.

2022-12-30 | GSE201288 | GEO

Lymphocyte Immune Response and T Cell Differentiation in Fontan Patients with protein-losing enteropathy.

Project description:BackgroundProtein-losing enteropathy (PLE) is a severe complication of the Fontan circulation. There is increasing discussion about whether lymphatic dysregulation is involved as pathomechanism of PLE. This investigation focuses on the interplay between alteration of lymphatic cells and immunologic pathway alterations.MethodsMicro-ribonucleic acid (miRNA) expression profiling was performed in 49 patients (n = 10 Fontan patients with PLE, n = 30 Fontan patients without PLE, and n = 9 patients with dextro-transposition of the great arteries (dTGA). miRNA pathway analysis was performed to identify significantly enriched pathways. To determine lymphocyte populations and subtypes multiparameter flow cytometry was used.ResultsmiRNAs pathway analysis of Fontan patients with PLE revealed 20 significantly changed networks of which four of the ten largest were associated with immunologic processes. This finding is supported by significant T cell deficiency with decreased CD4+ count (p = 0.0002), altered CD4 +/CD8+ ratio, and significantly modified CD4+ (p < 0.0001) and CD8+ (p = 0.0002) T cell differentiation toward effector and terminal differentiated T cells in Fontan patients with PLE. Analyses of CD4+ T cell subsets demonstrated significantly increased frequencies of CD4+ CD25+ CD127- regulatory T cells (Treg) in Fontan patients with PLE (p = 0.0011).ConclusionPLE in Fontan patients is associated with severe lymphopenia, T cell deficiency, significant alterations of T cell differentiation, and increased Treg frequency reflecting an immune status of chronic inflammation and shortened protection against pathogens and autoimmunity. These cellular alterations seemed to be dysregulated by several miRNA controlled immunological pathways.

| S-EPMC7909601 | biostudies-literature

Single cell multiomics guided mechanistic understanding of Fontan-associated liver disease

Project description:Liver biopsy samples were from patients with Fontan circulation (FC) and healthy patients undergoing resection or transplant for hepatoblastoma. We used snRNA-ATAC-seq to generate the transcriptomic and epigenomic atlas of human FALD.

2024-01-24 | GSE223843 | GEO

Transcriptomic analysis of intestinal biopsies in Zambian adults with environmental enteropathy

Project description:Study of adults with environmental enteropathy from residential area of Lusaka, Zambia

2021-07-15 | GSE179933 | GEO

Transcriptomic Analysis of Circulating Extracellular Vesicles and Serum during the Perioperative period of Fontan and Glenn Surgery

Project description:Single-ventricle defects are palliatively corrected using the Glenn and Fontan procedures that provide lifesaving relief but lead to early mortality rates and poor prognosis post-operatively. The pathophysiology of these complications is diverse, and there are no clear predictors for these outcomes. As such, we aimed to identify novel biomarkers for single-ventricle associated outcomes through the characterization of the serum transcriptome and small extracellular vesicles (sEVs). We report on molecular responses in serum and sEVs pre-operatively and post-operatively in patients undergoing either Glenn or Fontan operations. We found that transcriptomes of serum RNA and sEV RNA are distinctly different, whereas differences between the Fontan and Glenn transcriptomes did not show any significant changes. An in vitro wound healing assay further confirmed that post-operative sEVs have higher angiogenic potential. Moreover, we used a partial-least square regression model to identify 100 RNAs and 50 microRNAs that are involved in angiogenesis-related pathways and accurately predict our wound healing results and compared them with our previously published models of ovine Fontan surgery. Lastly, an EV-origin analysis showed decreased secretion of sEV from cardiac tissue in post-operative samples and increased secretion of sEVs from stomach and nervous tissue. Overall, this study provided evidence that the circulating sEVs transcriptome are potent biomarkers and demonstrated the role of sEVs as a possible mediator for formation of veno-venous collaterals.

2024-12-20 | GSE269879 | GEO

Gene expression in duodenal biopsy samples from CVID enteropathy patients and healthy controls

Project description:A subgroup of CVID patients presents with gastrointestinal complications (enteropathy), which manifests in the duodenum as celiac like-diese ase. CVID enteropathy patients can present with severe histopathology in form of villous atrophy (CVID VA) or without VA (CVID noVA). RNAseq data from CVID VA and CVID noVA derived duodenal tissues were compared to each other and to healthy controls.

2023-02-10 | GSE189820 | GEO

Single-cell profiling of environmental enteropathy reveals epithelial and immune dynamics

Project description:Here, we use the single-cell RNA-sequencing platform Seq-Well to generate a cellular atlas of environmental enteropathy in the proximal small intestine

2024-03-13 | GSE168883 | GEO

Protein losing enteropathy after the Fontan operation.

Project description:The Fontan or Fontan Kreutzer procedure is the culmination of staged, surgical palliation of functional single ventricle congenital heart disease, offering the potential for survival and good quality of life well into adulthood. As more patients with Fontan circulation age, a variety of complications involving almost every organ system may occur. Protein-losing enteropathy is a major cause of morbidity and mortality after the Fontan operation, occurring more often in patients with adverse hemodynamics and presenting weeks to years after Fontan surgery. The causes are not well understood, but likely include a combination of lymphatic insufficiency, high central venous pressure, loss of heparan sulfate from intestinal epithelial cells, abnormal mesenteric circulation, and intestinal inflammation. A comprehensive evaluation including multimodality imaging and cardiac catheterization is necessary to diagnose and treat any reversible causes. In advanced cases, early referral for heart transplantation evaluation or lymphatic decompression procedures (if the single ventricle function remains adequate) is indicated. Despite the improvement in detection and management options, the mortality remains high. Standardization of protein-losing enteropathy definition and management strategies will help facilitate interpretation of research and clinical experience, potentially fostering the identification of new therapies. Based on the published data, this review suggests a standardized approach to diagnosis and treatment.

| S-EPMC11657892 | biostudies-literature

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