title: Telomere dysfunction in peripheral blood lymphocytes from patients with primary sclerosing cholangitis and inflammatory bowel disease.
abstract: OBJECTIVE
  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  In this prospective study, peripheral blood was withdrawn from patients with primary sclerosing cholangitis (N=20), inflammatory bowel disease (N=20) and healthy controls (N=20), and lymphocytes were isolated.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).
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  NCT02247622.
authors.affiliation: Gastroenterology and Hepatology Institute, Meir Medical Center, Kfar Saba, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address: ido.laish@gmail.com.
authors.forename: Ido
authors.initials: I
authors.lastname: Laish
authors.affiliation: Genetic Institute, Meir Medical Center, Kfar Saba, Israel; Faculty of Life Sciences, Bar Ilan University, Ramat Gan, Israel.
authors.forename: Hila
authors.initials: H
authors.lastname: Katz
authors.affiliation: Gastroenterology and Hepatology Institute, Meir Medical Center, Kfar Saba, Israel.
authors.forename: Assaf
authors.initials: A
authors.lastname: Stein
authors.affiliation: Faculty of Life Sciences, Bar Ilan University, Ramat Gan, Israel.
authors.forename: Meytal
authors.initials: M
authors.lastname: Liberman
authors.affiliation: Gastroenterology and Hepatology Institute, Meir Medical Center, Kfar Saba, Israel.
authors.forename: Timna
authors.initials: T
authors.lastname: Naftali
authors.affiliation: Gastroenterology and Hepatology Institute, Meir Medical Center, Kfar Saba, Israel.
authors.forename: Yona
authors.initials: Y
authors.lastname: Kitay-Cohen
authors.affiliation: Department of Obstetrics and Gynecology, Meir Medical Center, Kfar Saba, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Tal
authors.initials: T
authors.lastname: Biron-Shental
authors.affiliation: Gastroenterology and Hepatology Institute, Meir Medical Center, Kfar Saba, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Fred M
authors.initials: FM
authors.lastname: Konikoff
authors.affiliation: Genetic Institute, Meir Medical Center, Kfar Saba, Israel; Faculty of Life Sciences, Bar Ilan University, Ramat Gan, Israel.
authors.forename: Aliza
authors.initials: A
authors.lastname: Amiel
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D015209:Cholangitis, Sclerosing / Q000097:blood*; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015212:Inflammatory Bowel Diseases / Q000097:blood*; D007557:Israel; D008214:Lymphocytes / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D019098:Telomerase / Q000097:blood*; D016615:Telomere / Q000235:genetics*; D062606:Tertiary Care Centers
chemical_list: D019098:Telomerase
keywords: Genetic instability; Primary sclerosing cholangitis; Telomere length