TY - JOUR
T1 - Telomere dysfunction in peripheral blood mononuclear cells from patients with primary biliary cirrhosis
AU - Invernizzi, Pietro
AU - Bernuzzi, Francesca
AU - Lleo, Ana
AU - Pozzoli, Vanila
AU - Bignotto, Monica
AU - Zermiani, Paola
AU - Crosignani, Andrea
AU - Battezzati, Pier Maria
AU - Zuin, Massimo
AU - Podda, Mauro
AU - Raggi, Chiara
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
KW - Autoimmune disease
KW - Primary biliary cirrhosis
KW - Telomere dysfunction
UR - http://www.scopus.com/inward/record.url?scp=84895544733&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84895544733&partnerID=8YFLogxK
U2 - 10.1016/j.dld.2013.11.008
DO - 10.1016/j.dld.2013.11.008
M3 - Article
C2 - 24378524
AN - SCOPUS:84895544733
VL - 46
SP - 363
EP - 368
JO - Digestive and Liver Disease
JF - Digestive and Liver Disease
SN - 1590-8658
IS - 4
ER -