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

Invernizzi, P.; Bernuzzi, F.; Lleo, A.; Pozzoli, V.M.; Bignotto, M.; Zermiani, P.; Crosignani, A.; Battezzati, P.M.; Zuin, M.; Podda, M.; Raggi, C.

doi:10.1016/j.dld.2013.11.008

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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
Autori:	INVERNIZZI, PIETRO BERNUZZI, FRANCESCA LLEO DE NALDA, ANA POZZOLI, VANILA MARIA BIGNOTTO, MONICA ZERMIANI, PAOLA EUGENIA A. Crosignani BATTEZZATI, PIER MARIA ZUIN, MASSIMO PODDA, MAURO C. Raggi mostra contributor esterni nascondi contributor esterni
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
Rivista:	DIGESTIVE AND LIVER DISEASE
Tipologia:	Article (author)
Digital Object Identifier (DOI):	http://dx.doi.org/10.1016/j.dld.2013.11.008
Appare nelle tipologie:	01 - Articolo su periodico

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