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Telomere dysfunction in peripheral blood lymphocytes from patients with primary sclerosing cholangitis and inflammatory bowel disease.
Published: 05/13/2015, Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver
Background And Aims
Primary sclerosing cholangitis and inflammatory bowel disease are two associated, chronic inflammatory, pre-malignant conditions. We hypothesized that patients with these disorders may harbour telomere dysfunction as a marker of chromosomal instability. The aim of our study was to compare parameters of the telomere-telomerase system in these cohorts.
Methods
In this prospective study, peripheral blood was withdrawn from patients with primary sclerosing cholangitis (N=20), inflammatory bowel disease (N=20) and healthy controls (N=20), and lymphocytes were isolated. Telomere length was quantified as a function of the signal intensity and telomere number. Random aneuploidy and telomere capture were determined by fluorescence in situ hybridization technique with specific probes.
Results
Patients with inflammatory bowel disease had higher measures of intestinal disease activity than patients with primary sclerosing cholangitis. Despite this, shorter telomere length and telomere aggregates, especially the fusion of 2-5 telomeres, were observed at significantly higher rate in patients with primary sclerosing cholangitis relative to inflammatory bowel disease or healthy controls. Rates of aneuploidy and telomere capture were higher in the two probes in both diseases compared to controls (p<0.001).
Conclusion
Dysfunction of telomeres was demonstrated in primary sclerosing cholangitis patients more than inflammatory bowel disease and healthy controls patients, which attests to genetic instability and immunosenescence.
Trial Registration Number
NCT02247622.
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