Dataset Information

Tissue factor in ulcerative colitis, with and without concomitant primary sclerosing cholangitis.

ABSTRACT: Background: Ulcerative colitis (UC) in patients with the severe disease primary sclerosing cholangitis (PSC) constitutes a distinct clinical phenotype (PSC-UC) with a high incidence of colorectal cancer. Today, PSC-UC diagnosis is built on clinical observations only. Tissue factor (TF) has a potential use in UC diagnostics, and also in colorectal cancer prognostication. Here we evaluate TF expression in an inflammatory bowel disease (IBD) cohort, with special focus on differences between UC and PSC-UC patients.Materials and methods: Colonic biopsies from UC (n?=?23), PSC (n?=?24), and healthy controls (n?=?11) were stained for TF by immunohistochemistry. Mononuclear cell contribution to TF expression was verified using flow cytometry.Results: TF was distributed at three distinct colonic locations: in subepithelial pericryptal sheath cells, in mononuclear cells, and in the intestinal stroma. In contrast to UC-where inflammation was accompanied with TF up-regulation-PSC-UC activity remained low during inflammation. Stromal TF positivity was found exclusively in ongoing inflammation.Conclusion: Our study provides additional support for a divergent pathogenesis in PSC-UC, with an inflammatory environment that differs from classical UC. Stromal TF emerges as a new marker of colonic inflammation.

SUBMITTER: Vessby J

PROVIDER: S-EPMC6968534 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Tissue factor in ulcerative colitis, with and without concomitant primary sclerosing cholangitis.

Vessby Johan J Lampinen Maria M Åberg Mikael M Rorsman Fredrik F Siegbahn Agneta A Wanders Alkwin A Carlson Marie M

Upsala journal of medical sciences 20191127 4

<b>Background:</b> Ulcerative colitis (UC) in patients with the severe disease primary sclerosing cholangitis (PSC) constitutes a distinct clinical phenotype (PSC-UC) with a high incidence of colorectal cancer. Today, PSC-UC diagnosis is built on clinical observations only. Tissue factor (TF) has a potential use in UC diagnostics, and also in colorectal cancer prognostication. Here we evaluate TF expression in an inflammatory bowel disease (IBD) cohort, with special focus on differences between ...[more]

PMID: 31774347

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Project description:ObjectivesThe clinical/colonoscopic features of ulcerative colitis (UC) associated with primary sclerosing cholangitis (PSC), the prognostic impact of UC, and the utility of UC screening in PSC patients are unknown. We characterized UC associated with PSC and assessed UC's impact on the prognosis of PSC and the importance of colonoscopic UC screening in PSC patients.MethodsWe retrospectively analyzed the cases of 77 patients treated for PSC at a single center (April 2000-July 2019). We reviewed the clinical/colonoscopic profiles of the concurrent UC patients and compared the clinical profiles, survival, and primary causes of death between the patients with/without UC (n = 35/n = 42). The details of all patients' colonoscopies were reviewed.ResultsThe concurrent UC group: 17 men, 18 women, diagnosed with PSC at the mean (SD) age of 36 (17) years; 21 patients (60%) had no UC symptoms. Colonoscopy revealed pancolitis in all patients, predominantly affecting the right-sided colon in 30 patients (86%). Lesions were scattered. Backwash ileitis (n = 13, 37%) and rectal sparing (n = 18, 51%) were observed. Most patients had mild UC; some had moderate or more severe UC (median Ulcerative Colitis Endoscopic Index of Severity (UCEIS) score 2; range, 1-5). Ludwig's stage determined by liver biopsy did not correlate with the Mayo endoscopic score for UC. The patients with UC were diagnosed with PSC at a significantly younger age than those without UC (mean (SD), 36 [17] years vs. 55 [19] years, p < 0.0001) and had a significantly higher 5-year survival rate (97.1% vs. 70.5%, p = 0.0028). UC was detected in 19 of 34 asymptomatic patients (56%) who underwent colonoscopy screening.ConclusionsOur cohort's clinical/colonoscopic features of UC associated with PSC are more moderate or severe UC than previous cases. The coexistence of UC might affect the prognosis of PSC. In this regard, colonoscopy in PSC patients is an important examination for determining prognosis. There is also asymptomatic UC in patients with PSC. In this regard, screening for colonoscopy in PSC patients is essential. When a diagnosis of PSC is made, immediate colonoscopy is a priority with UC complications in mind.

Project description:Background: Patients suffering from primary sclerosing cholangitis (PSC) often also have ulcerative colitis (UC). Cross-disease genetic and microbiome studies across PSC und UC patients indicated that UC in PSC is a separate disease entity from primary UC, but expression studies for PSC are lacking. In this study, we performed a molecular comparison of whole blood expression levels in PSC only, PSC patients with additional UC diagnosis (PSC/UC), and UC, using a large collection of whole blood transcriptome data. Methods: We conducted whole blood RNA-Seq experiments for 495 UC patients, 220 PSC patients (of whom 177 have also a UC diagnosis), and 320 healthy controls from Germany and Norway. Differential expression analyses, gene ontology and coexpression analyses and random forest machine learning were performed to identify genes, ontologies and transcriptional features that discriminate diagnoses. Results: The blood transcriptome in UC and PSC is dominated by neutrophil activation genes. In UC, but not in PSC (neither PSC alone nor PSC/UC), there is upregulation of genes for ribosomes, mitochondria and energy metabolism genes in conjunction with antibody transcript expression. In PSC, there is an increase in modules related to apoptosis and expression of genes of interferon-I-related ontologies. Random forest analysis could poorly discriminate PSC alone from PSC/UC (AUROC 0.56), but could discriminate PSC, UC, and controls with high accuracy (AUROC UC vs controls 0.95, PSC vs controls 0.88, UC vs PSC 0.986). The main coexpression modules are enriched in neutrophil degranulation and antibody production genes relevant for distinguishing PSC, UC, and controls. Conclusions: PSC and UC share neutrophil-related transcriptional upregulation in whole blood (e.g. S100A12). UC is characterised by upregulation of modules involved in antibody production (MZB1, IGJ) and increased metabolic activity (PDK4, ribosomal genes), while PSC differs from UC by interferon (IFIT1) and apoptosis upregulation (G0S2). Supported by machine learning results, PSC and UC are interpreted as molecularly separate entities, while PSC/UC and PSC are indistinguishable.

Dataset Information

Tissue factor in ulcerative colitis, with and without concomitant primary sclerosing cholangitis.

Publications

Tissue factor in ulcerative colitis, with and without concomitant primary sclerosing cholangitis.

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