Expressie van CCL25 en CCR9 bij inflammatoire darmziekten en primaire scleroserende cholangitis.

Rationale:

Primary sclerosing cholangitis (PSC) is a rare chronic cholestatic disease of unknown cause. Chronic inflammation leads to bile duct destruction resulting in liver failure. PSC is regarded as an immune dysbalance disease. PSC has a strong association with IBD, especially ulcerative colitis and some consider PSC as an extraintestinal manifestation of IBD. The gut-homing lymphocyte paradigm offers a plausible explanation linking the gut and liver in PSC.



Primary objective:

To demonstrate and compare expression of CCL25 and CCR9+ lymphocytes in peripheral blood and colon of PSC-, PSC/IBD-, IBD-, gastroenteritis patients and controls.



Study design:

Exploratory case control study.



Study population:

1. Newly diagnosed PSC patients screened for IBD, ≥18 yr old;

2. a. Newly diagnosed UC patients, ≥18 yr old;

2. b. Infectious enterocolitis patients (bacterial/viral/parasitic), ≥18 yr old;

3. PSC/UC surveillance patients, ≥18 yr old;

4. UC surveillance patients, ≥18 yr old;

5. Controls referred for CRC screening, ≥18 yr old.



Main study parameters/endpoints:

1. Expression of CCL25 in human colon by immunohistochemistry;

2. Difference in proportion of CCL25 and/or CCR9+ lymphocytes in double stained colonic biopsies between patients and controls;

3. Quantitative analyses of CCL25 mRNA expression in colon of patients and controls;

4. Quantitative analyses α4β7/CCR9+ T cells in peripheral blood.



Nature and extent of the burden and risks associated with participation, benefit and group relatedness:

Colonic biopsies are obtained during surveillance colonoscopy at the Department of Gastroenterology and Hepatology AMC. 8 specimens at 3 levels, 24 specimens in total per patient. During standard surveillance colonoscopy procedure 32 biopsies are obtained for pathological analyses. The additive burden consists of 24 additional biopsies. One extra blood sample is drawn prior to colonoscopy.

Primary sclerosing cholangitis (PSC) is a rare chronic cholestatic disease of unknown cause. Chronic inflammation leads to bile duct destruction resulting in liver failure. PSC is regarded as an immune dysbalance disease. PSC has a strong association with IBD, especially ulcerative colitis and some consider PSC as an extraintestinal manifestation of IBD. The gut-homing lymphocyte paradigm offers a plausible explanation linking the gut and liver in PSC.

One timepoint: PBMC isolation and biopsy collection during colonoscopy.

Ileal and colonic biopsies during colonoscopy.