The aim of this project is to characterize the composition and activity of lymphocytes immune cell subsets and cholangiocytes in active inflammation in the central/extrahepatic bile ducts through surface markers and an in-depth transcriptomic…
ID
Source
Brief title
Condition
- Hepatic and hepatobiliary disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To characterize the disease specific composition and activity of immune cell
subsets and cholangiocytes in active inflammation in the central/extrahepatic
bile ducts of PSC patients and *normal* bileduct tissue using surface markers
and in-depth transcriptomic analysis.
Secondary outcome
1. To characterize immune cell subsets between peripheral blood of PSC patients
and compare these to the bile duct derived subsets in relation to samples taken
from *healthy* bileduct epithelium.
2. To align the outcome of this transcriptomic analysis with known drug target
genes.
3. To align the outcome of this transcriptome analysis with previously
identified inflammatory patterns in the colon of IBD patients with and without
PSC
Background summary
Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease,
for which there is currently no therapy that can halt disease progression. PSC
is generally regarded as an immune-mediated disease, but disease etiology and
pathogenesis is still largely unknown. This is mainly due to the rarity of the
disease and the fact that the diseased tissue is hidden deep in the body. In
order to deep-dive into the immune dysregulation that characterizes the chronic
inflammation in and the progressive fibrosis around the bile ducts, it is
imperative to study the two cell types that presumably play a central role in
disease initiation and perpetuation of inflammation: the cholangiocyte as
antigen presenting cell, and lymphocyte subsets such as T-lymphocytes and
natural killer cells as effector cells. The novel technique of single cell RNA
sequencing combined with advanced bioinformatic analysis can yield a myriad of
information about development, function, behavior, and interaction of cells in
their relevant microenvironment. To this end, tissue must be harvested not from
explanted livers, in which the original inflammation has evolved to fibrosis,
but from early stage disease patients, in whom the inflammatory process is
still ongoing. Using what is known as the *last frontier of endoscopy*, i.e.
cholangioscopy, it is possible to gain access to the bile ducts and sample the
tissue of interest: the mucosa of the bile duct. Single cell RNA sequencing
technology provides a unique opportunity to do comprehensive analysis from the
minute amounts of tissue that are obtained through cholangioscopy.
Study objective
The aim of this project is to characterize the composition and activity of
lymphocytes immune cell subsets and cholangiocytes in active inflammation in
the central/extrahepatic bile ducts through surface markers and an in-depth
transcriptomic analysis. Furthermore In addition, immune cell composition
lymphocyte subsets in the colon and peripheral blood will be studied and
compared to the liver bile duct derived subsets.
Study design
Multi-center, cross-sectional case-control study
Study burden and risks
The is a very limited risk of complications as the biopsies for this study will
be taken only when there is also a clinical/diangostic indication for biopsies
with the same low-risk technique (spy-bite or transpapillary biopsy) as will be
done to exclude malignancy and perform.
Meibergdreef 9
Amsterdam 1105 AZ
NL
Meibergdreef 9
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
In order to be eligible to participate in this study, a subject must meet all
of the following criteria:
Cases:
- established diagnosis of large duct PSC and concurrent inflammatory bowel
disease.
- Patients should be able to give written informed consent
- age >=18 year
- Child-Pugh-Turcott score <7
- Clinical indication for ERC, i.e. progressive complaints together with
increase in biochemical cholestasis or suspicion of malignancy.
- Thickened bile duct wall at the location of interest as evidenced by
dedicated ultrasound or MRC.
Controls:
- A suspected diagnosis of (peri)hilar cholangiocarcinoma
- Clinical indication for ERC, i.e. cholestatic itch, pre-operative drainage
- Patients should be able to give written informed consent
- Age >=18 year
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded
from participation in this study:
Cases:
- signs of bacterial cholangitis
- mandatory anticoagulation
Controls:
- signs of bacterial cholangitis
- mandatory anticoagulation
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL80240.018.22 |