CD55 Deficiency, Early-Onset Protein-Losing Enteropathy and Thrombosis
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PROVIDER: PRJNA389487 | ENA |
REPOSITORIES: ENA
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Project description:CD55 Deficiency, Early-Onset Protein-Losing Enteropathy and Thrombosis
| PRJNA389488 | ENA
Project description:<p>We describe 11 patients from 8 families with homozygous LOF mutations in the complement regulatory protein CD55. Loss of CD55 is associated with increased complement activation, severe protein losing enteropathy accompanying a primary intestinal lymphangiectasia, and deep vein thrombotic events. We have named this disease CHAPLE after the principle components of the disease.</p>
| phs001376 | dbGaP
Project description:BackgroundStudies of monogenic gastrointestinal diseases have revealed molecular pathways critical to gut homeostasis and enabled the development of targeted therapies.MethodsWe studied 11 patients with abdominal pain and diarrhea caused by early-onset protein-losing enteropathy with primary intestinal lymphangiectasia, edema due to hypoproteinemia, malabsorption, and less frequently, bowel inflammation, recurrent infections, and angiopathic thromboembolic disease; the disorder followed an autosomal recessive pattern of inheritance. Whole-exome sequencing was performed to identify gene variants. We evaluated the function of CD55 in patients' cells, which we confirmed by means of exogenous induction of expression of CD55.ResultsWe identified homozygous loss-of-function mutations in the gene encoding CD55 (decay-accelerating factor), which lead to loss of protein expression. Patients' T lymphocytes showed increased complement activation causing surface deposition of complement and the generation of soluble C5a. Costimulatory function and cytokine modulation by CD55 were defective. Genetic reconstitution of CD55 or treatment with a complement-inhibitory therapeutic antibody reversed abnormal complement activation.ConclusionsCD55 deficiency with hyperactivation of complement, angiopathic thrombosis, and protein-losing enteropathy (the CHAPLE syndrome) is caused by abnormal complement activation due to biallelic loss-of-function mutations in CD55. (Funded by the National Institute of Allergy and Infectious Diseases and others.).
| S-EPMC6690356 | biostudies-literature
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
Project description:Study of adults with environmental enteropathy from residential area of Lusaka, Zambia
2021-07-15 | GSE179933 | GEO
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
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
Project description:Arterial and venous (A/V) thrombosis constitutes the greatest source of morbidity and mortality worldwide. Long considered as distinct entities, accumulating evidence indicates that A/V thrombosis can occur in the same populations suggesting that common mechanisms are likely operative. Although hyperactivation of the immune system is a common forerunner to the genesis of thrombotic events in both vascular systems, the key molecular control points remain poorly understood. Consequently, anti-thrombotic therapies targeting the immune system for therapeutic gain are lacking. Here we show that neutrophils are key effectors of both A/V thrombosis and can be targeted via novel immunoregulatory nanoparticles. Using antiphopholipid antibody syndrome (APS) as a model for devastating A/V thrombosis, we identified the transcription factor Krüppel-like factor 2 (KLF2) as a key regulator of neutrophil activation. Upon activation via genetic loss of KLF2 or administration of antiphospholipid antibodies, neutrophils cluster P-selectin glycoprotein ligand 1 (PSGL-1) via cortical actin remodeling, thereby increasing adhesion potential at thrombosis sites. Targeting clustered PSGL-1 using designer nanoparticles attenuates neutrophil-mediated A/V thrombosis in APS and KLF2 knockout models, illustrating the importance and feasibility of targeting activated neutrophils to prevent pathological thrombosis. Together, our results demosntrate a role for activated neutrophils to prevent pathological thrombosis. Together, our results demonstrate a role for activated neutorphils in both arterial and venous thrombosis and identify key molecular events that serve as potential targets for therapeutics against diverse causes of immunothrombosis.
2022-09-12 | GSE208336 | GEO
Project description:Approximately 2–5% of adult-onset coeliac disease (CD) patients develops refractory coeliac disease (RCD). In contrast to RCD type I, RCD type II is characterised by the presence of aberrant small intestinal intraepithelial T-lymphocytes (IEL) expressing cytoplasmic CD3 but lacking surface expression of CD3, CD4 and CD8. Development of Enteropathy Associated T-cell Lymphoma (EATL) is directly associated with the presence of >20% aberrant IEL in RCD II patients and has a very poor prognosis. We report on an exceptional case of EATL presenting as leukemic ascites and on the unique opportunity to perform extensive phenotypic and genomic analysis of this malignancy. Flow cytometric immunophenotyping of the ascitic EATL presentation showed CD30 expression typical for EATL and loss of the above mentioned surface markers similar to the aberrant IEL it originated from, as indicated by an identical monoclonal TCR-gamma rearrangement. In addition, expression of a substantial number of markers, including CD2, CD7, CD11a/CD18, CD52, CD103 and granzyme B was lost, which has not been reported sofar. Expression of proliferation markers Ki-67 en PCNA was clearly detected in the majority of EATL cells. Karyotype and comparative genomic hybridisation (CGH) analyses showed many genomic alterations, including chromosomal gains and losses up to 47Mb not previously reported for EATL. In conclusion, the current exceptional EATL presentation displays both immunophenotypic and genomic alterations not described previously and not included in the current WHO classifications of lymphoid malignancies. Comparative genomic hybridisation (CGH) analyses of an exceptional case of enteropathy associated T cell lymphoma
2010-06-17 | E-GEOD-17715 | biostudies-arrayexpress
Project description:Deep vein thrombosis (DVT) is a common clinical problem, but its cellular and molecular mechanisms remain incompletely understood. We performed single-cell RNA sequencing (scRNA-seq) on the vein wall of mouse inferior vena cava (IVC) ligation model of deep vein thrombosis (DVT), to analyze the transcriptomic changes in the vein wall during acute venous thrombosis.
2023-02-10 | GSE221978 | GEO