Immune-mediated diseases in primary sclerosing cholangitis

2011 ◽  
Vol 43 (10) ◽  
pp. 802-806 ◽  
Author(s):  
Laetitia E. Lamberts ◽  
Marcel Janse ◽  
Elizabeth B. Haagsma ◽  
Arie P. van den Berg ◽  
Rinse K. Weersma
Keyword(s):  
Primary Sclerosing Cholangitis ◽  
Sclerosing Cholangitis ◽  
Immune Mediated

scholarly journals Administration of Human MSC-Derived Extracellular Vesicles for the Treatment of Primary Sclerosing Cholangitis: Preclinical Data in MDR2 Knockout Mice

2020 ◽  
Vol 21 (22) ◽  
pp. 8874
Author(s):  
Roberta Angioni ◽  
Bianca Calì ◽  
Vasanthy Vigneswara ◽  
Marika Crescenzi ◽  
Ana Merino ◽  
...  
Keyword(s):  
Primary Sclerosing Cholangitis ◽  
Extracellular Vesicles ◽  
Sclerosing Cholangitis ◽  
Serum Levels ◽  
Portal Triad ◽  
Immune Mediated ◽  
Nfkb Activation ◽  
Effective Therapeutic Strategy ◽  
Progressive Liver Disease ◽  
Clinical Experiments

Primary Sclerosing Cholangitis (PSC) is a progressive liver disease for which there is no effective medical therapy. PSC belongs to the family of immune-mediated biliary disorders and it is characterized by persistent biliary inflammation and fibrosis. Here, we explored the possibility of using extracellular vesicles (EVs) derived from human, bone marrow mesenchymal stromal cells (MSCs) to target liver inflammation and reduce fibrosis in a mouse model of PSC. Five-week-old male FVB.129P2-Abcb4tm1Bor mice were intraperitoneally injected with either 100 µL of EVs (± 9.1 × 109 particles/mL) or PBS, once a week, for three consecutive weeks. One week after the last injection, mice were sacrificed and liver and blood collected for flow cytometry analysis and transaminase quantification. In FVB.129P2-Abcb4tm1Bor mice, EV administration resulted in reduced serum levels of alkaline phosphatase (ALP), bile acid (BA), and alanine aminotransferase (ALT), as well as in decreased liver fibrosis. Mechanistically, we observed that EVs reduce liver accumulation of both granulocytes and T cells and dampen VCAM-1 expression. Further analysis revealed that the therapeutic effect of EVs is accompanied by the inhibition of NFkB activation in proximity of the portal triad. Our pre-clinical experiments suggest that EVs isolated from MSCs may represent an effective therapeutic strategy to treat patients suffering from PSC.

scholarly journals Primary Sclerosing Cholangitis: Therapeutic Options and Surveillance Management

2016 ◽  
Vol 9 ◽  
pp. CGast.S38451 ◽  
Author(s):  
Aditi Kumar ◽  
Daniel Wheatley ◽  
Amar Puttanna
Keyword(s):  
Primary Sclerosing Cholangitis ◽  
Sclerosing Cholangitis ◽  
Disease Recurrence ◽  
Evidence Base ◽  
Therapeutic Options ◽  
Weak Evidence ◽  
Immune Mediated ◽  
Metabolic Bone ◽  
Bowel Disorders ◽  
Risk Of Disease

Primary sclerosing cholangitis is a chronic immune-mediated liver disease. Though rare, it poses several clinical concerns for the managing physician. There are currently limited therapeutic options in the management of the condition and weak evidence base behind them. Endoscopic intervention is limited to those patients with obstructing stricture-related disease, and even liver transplantation has a risk of disease recurrence. Surveillance for inflammatory bowel disorders, metabolic bone disease, and malignancy is paramount when managing such patients. This article provides an overview of the condition with further focus on current therapeutic options and guidance on surveillance management.

Primary sclerosing cholangitis

2010 ◽  
pp. 2468-2473
Author(s):  
R.W. Chapman ◽  
K.D. Williamson
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Bowel Disease ◽  
Weight Loss ◽  
Primary Sclerosing Cholangitis ◽  
Sclerosing Cholangitis ◽  
Close Association ◽  
Biliary Tree ◽  
Cholestatic Liver Disease ◽  
Immune Mediated ◽  
Inflammatory Bowel

Case History—A 60 yr old woman, known to have long standing colitis, now presenting with abdominal pain and weight loss. Primary sclerosing cholangitis is a chronic cholestatic liver disease caused by diffuse inflammation and fibrosis that can involve the entire biliary tree. The cause is unknown, but presumed to be immune mediated, and there is a very close association with inflammatory bowel disease, particularly ulcerative colitis....

scholarly journals Gene Expression by PBMC in Primary Sclerosing Cholangitis: Evidence for Dysregulation of Immune Mediated Genes

2006 ◽  
Vol 13 (2-4) ◽  
pp. 265-271 ◽  
Author(s):  
Christopher A. Aoki ◽  
Kevin Dawson ◽  
Thomas P. Kenny ◽  
M. Eric Gershwin ◽  
Christopher L. Bowlus
Keyword(s):  
Gene Expression ◽  
Primary Sclerosing Cholangitis ◽  
Messenger Rna ◽  
Sclerosing Cholangitis ◽  
Mononuclear Cells ◽  
Differentially Expressed ◽  
Peripheral Blood Mononuclear ◽  
Immune Mediated ◽  
Membrane Spanning ◽  
Immune Related Genes

Primary sclerosing cholangitis (PSC) is a chronic disease of the bile ducts characterized by an inflammatory infiltrate and obliterative fibrosis. The precise role of the immune system in the pathogenesis of PSC remains unknown. We used RNA microarray analysis to identify immune-related genes and pathways that are differentially expressed in PSC. Messenger RNA (mRNA) from peripheral blood mononuclear cells (PBMC) was isolated from both patients with PSC and age and sex matched healthy controls. Samples from 5 PSC patients and 5 controls were analyzed by microarray and based upon rigorous statistical analysis of the data, relevant genes were chosen for confirmation by RT-PCR in 10 PSC patients and 10 controls. Using unsupervised hierarchical clustering, gene expression in PSC was statistically different from our control population. Interestingly, genes within the IL-2 receptor beta, IL-6 and MAP Kinase pathways were found to be differently expressed in patients with PSC compared to controls. Further, individual genes, TNF-α induced protein 6 (TNFaip6) and membrane-spanning 4-domains, subfamily A (ms4a) were found to be upregulated in PSC while similar to Mothers against decapentaplegic homolog 5 (SMAD 5) was downregulated. In conclusion, several immune-related pathways and genes were differentially expressed in PSC compared to control patients, giving further evidence that this disease is systemic and immune-mediated.

Timing, Management, and Outcomes of Liver Transplantation in Primary Sclerosing Cholangitis

2017 ◽  
Vol 37 (04) ◽  
pp. 305-313 ◽  
Author(s):  
Cynthia Levy ◽  
Eric Martin
Keyword(s):  
Liver Transplantation ◽  
Liver Disease ◽  
Primary Sclerosing Cholangitis ◽  
Graft Survival ◽  
Sclerosing Cholangitis ◽  
Cholestatic Liver Disease ◽  
Biliary Cirrhosis ◽  
Immune Mediated ◽  
End Stage ◽  
Patient And Graft Survival

AbstractPrimary sclerosing cholangitis (PSC) is a chronic, immune-mediated cholestatic liver disease that often progresses to secondary biliary cirrhosis and end-stage liver disease. Short of liver transplantation (LT), there is no effective treatment for PSC. PSC accounts for approximately 5% of total adult LTs in the US and is currently the fifth most common indication for LT. Patient and graft survival for PSC is among the highest for all indications for LT. The main factors that impact outcomes after LT for PSC include biliary strictures, rejection, and recurrence of PSC. Recurrent PSC (rPSC) develops in 20% of LT recipients within 5 years of LT and is associated with negative patient and graft survival. LT is a viable option for recipients who develop rPSC and progress to graft failure.

Immune-Mediated Diseases in Primary Sclerosing Cholangitis

2011 ◽  
Vol 140 (5) ◽  
pp. S-919
Author(s):  
Laetitia E. Lamberts ◽  
Marcel Janse ◽  
Elizabeth B. Haagsma ◽  
Arie P. Van den Berg ◽  
Rinse K. Weersma
Keyword(s):  
Primary Sclerosing Cholangitis ◽  
Sclerosing Cholangitis ◽  
Immune Mediated

scholarly journals Interference with the lower gut–liver axis induces remission of primary sclerosing cholangitis in a patient with ulcerative colitis

2018 ◽  
Vol 5 (1) ◽  
pp. e000239
Author(s):  
John Ong ◽  
Leila Mebarek ◽  
Michael Bath ◽  
Carla Swift ◽  
Babur Javaid ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Primary Sclerosing Cholangitis ◽  
Sclerosing Cholangitis ◽  
Subtotal Colectomy ◽  
Rectal Stump ◽  
Current Evidence ◽  
Treatment Resistant ◽  
Full Remission ◽  
Complex Interactions ◽  
Immune Mediated

The gut–liver axis describes the complex interactions between gut microbiota, the small and large bowel, the immune system and the liver. Current evidence associates abnormalities within the gut–liver axis with liver disease such as primary sclerosing cholangitis (PSC). PSC is believed to be an immune-mediated disease though the exact mechanism of its pathogenesis remains unknown. Here, we report a case of a 66 -year-old woman with treatment-resistant ulcerative colitis and PSC which continued to be active following subtotal colectomy. Interestingly, her PSC achieved full remission after proctectomy for treatment-resistant proctitis in the rectal stump. This case report supports existing hypotheses that PSC is an immune-mediated disease triggered by antigens within the gut. More notably, it suggests the yet unidentified pathogens may be localised to the lower gastrointestinal tract including the rectum.

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