Telomere dysfunction in peripheral blood mononuclear cells from patients with primary biliary cirrhosis

Pietro Invernizzi, Francesca Bernuzzi, Ana Lleo, Vanila Pozzoli, Monica Bignotto, Paola Zermiani, Andrea Crosignani, Pier Maria Battezzati, Massimo Zuin, Mauro Podda, Chiara Raggi

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8 Scopus citations

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. Aim: To evaluate the clinical significance of telomerase activity and telomere length in peripheral blood mononuclear cells from patients with primary biliary cirrhosis. Study design: 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±1.5kb) and controls (6.2±1.4kb, 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)363-368
Number of pages6
JournalDigestive and Liver Disease
Volume46
Issue number4
DOIs
StatePublished - 2014
Externally publishedYes

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Keywords

  • Autoimmune disease
  • Primary biliary cirrhosis
  • Telomere dysfunction

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology

Cite this

Invernizzi, P., Bernuzzi, F., Lleo, A., Pozzoli, V., Bignotto, M., Zermiani, P., Crosignani, A., Battezzati, P. M., Zuin, M., Podda, M., & Raggi, C. (2014). Telomere dysfunction in peripheral blood mononuclear cells from patients with primary biliary cirrhosis. Digestive and Liver Disease, 46(4), 363-368. https://doi.org/10.1016/j.dld.2013.11.008