title: Telomere dysfunction in peripheral blood mononuclear cells from patients with primary biliary cirrhosis.
abstract: BACKGROUND
  Chromosomal instability in peripheral blood mononuclear cells has a role in the onset of primary biliary cirrhosis. We hypothesized that patients with primary biliary cirrhosis may harbour telomere dysfunction, with consequent chromosomal instability and cellular senescence.
  
  
  OBJECTIVE
  To evaluate the clinical significance of telomerase activity and telomere length in peripheral blood mononuclear cells from patients with primary biliary cirrhosis.
  
  
  METHODS
  In this population-based case control study, 48 women with primary biliary cirrhosis (25 with cirrhosis), 12 with chronic hepatitis C matched by age and severity of disease, and 55 age-matched healthy women were identified. Mononuclear cells from the peripheral blood of patients and controls were isolated. Telomere length and telomerase activity were measured.
  
  
  RESULTS
  Telomere length and telomerase activity did not differ between cases (5.9 ± 1.5 kb) and controls (6.2 ± 1.4 kb, pc=0.164). Telomere shortening and advanced-stage disease strongly correlated with telomerase activity. Patients with advanced disease retained significantly less telomerase activity than those with early-stage disease (0.6 ± 0.9 OD vs. 1.5 ± 3.7 OD, p=0.03). Telomere loss correlated with age, suggesting premature cellular ageing in patients with primary biliary cirrhosis.
  
  
  CONCLUSIONS
  Our data strongly support the telomere hypothesis of human cirrhosis, indicating that telomere shortening and telomerase activity represent a molecular mechanism in the evolution of human cirrhosis in a selected population of patients.
authors.affiliation: Liver Unit and Center for Autoimmune Liver Diseases Humanitas Clinical and Research Center, Rozzano, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Invernizzi
authors.affiliation: Liver Unit and Center for Autoimmune Liver Diseases Humanitas Clinical and Research Center, Rozzano, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Bernuzzi
authors.affiliation: Liver Unit and Center for Autoimmune Liver Diseases Humanitas Clinical and Research Center, Rozzano, Italy.
authors.forename: Ana
authors.initials: A
authors.lastname: Lleo
authors.affiliation: Gastroenterology and Liver Unit, San Paolo Hospital Medical School, University of Milan, Milan, Italy.
authors.forename: Vanila
authors.initials: V
authors.lastname: Pozzoli
authors.affiliation: Gastroenterology and Liver Unit, San Paolo Hospital Medical School, University of Milan, Milan, Italy; Department of Human Morphology and Biomedical Sciences, University of Milan, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Bignotto
authors.affiliation: Gastroenterology and Liver Unit, San Paolo Hospital Medical School, University of Milan, Milan, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Zermiani
authors.affiliation: Gastroenterology and Liver Unit, San Paolo Hospital Medical School, University of Milan, Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Crosignani
authors.affiliation: Gastroenterology and Liver Unit, San Paolo Hospital Medical School, University of Milan, Milan, Italy.
authors.forename: Pier Maria
authors.initials: PM
authors.lastname: Battezzati
authors.affiliation: Gastroenterology and Liver Unit, San Paolo Hospital Medical School, University of Milan, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Zuin
authors.affiliation: Liver Unit and Center for Autoimmune Liver Diseases Humanitas Clinical and Research Center, Rozzano, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Podda
authors.affiliation: Liver Unit and Center for Autoimmune Liver Diseases Humanitas Clinical and Research Center, Rozzano, Italy. Electronic address: chiara.raggi@humanitasresearch.it.
authors.forename: Chiara
authors.initials: C
authors.lastname: Raggi
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D016922:Cellular Senescence / Q000235:genetics; D005260:Female; D019698:Hepatitis C, Chronic / Q000201:enzymology / Q000235:genetics; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000201:enzymology / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000201:enzymology / Q000235:genetics; D008105:Liver Cirrhosis, Biliary / Q000201:enzymology / Q000235:genetics*; D008875:Middle Aged; D019098:Telomerase / Q000378:metabolism*; D016615:Telomere / Q000378:metabolism*; D059505:Telomere Homeostasis / Q000235:genetics*; D059506:Telomere Shortening
chemical_list: D019098:Telomerase
keywords: Autoimmune disease; Primary biliary cirrhosis; Telomere dysfunction