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 ± 1.5 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. 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
Telomere dysfunction in peripheral blood mononuclear cells from patients with primary biliary cirrhosis / P. Invernizzi, F. Bernuzzi, A. Lleo, V. Pozzoli, M. Bignotto, P. Zermiani, A. Crosignani, P.M. Battezzati, M. Zuin, M. Podda, C. Raggi. - In: DIGESTIVE AND LIVER DISEASE. - ISSN 1590-8658. - 46:4(2014), pp. 363-368.
|Titolo:||Telomere dysfunction in peripheral blood mononuclear cells from patients with primary biliary cirrhosis|
|Parole Chiave:||autoimmune disease ; primary biliary cirrhosis ; Telomere dysfunction ; rheumatoid-arthritis ; chromosomal instability ; cellular senescence ; immune-system ; diseases ; length ; autoimmunity ; monosomy|
|Settore Scientifico Disciplinare:||Settore MED/09 - Medicina Interna|
|Data di pubblicazione:||2014|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.dld.2013.11.008|
|Appare nelle tipologie:||01 - Articolo su periodico|