Telomerase activity and telomere length of peripheral blood mononuclear cells in SLE patients.
ABSTRACT We evaluated the clinical significance of the telomerase activity and telomere length of peripheral blood mononuclear cells (PBMC) in systemic lupus erythematosus (SLE). PBMC were isolated from 55 patients with SLE and the telomerase activity was measured by TRAP assay. The telomere length of PBMC was also measured in 30 of these subjects. As a control group, 45 healthy adults with no particular clinical history were studied. The results were compared with clinical data. In patients with active SLE, the telomerase activity of PBMC was significantly increased compared with the control group. In patients with inactive SLE, the PBMC telomerase activity was not different compared with the controls in their 20s, 30s and 40s, but it was significantly increased compared with the controls in their 50s. In SLE patients, the telomerase activity of PBMC was significantly correlated with modified SLEDAI. The telomere length of PBMC in younger SLE patients tended to be shorter than that in the controls, but no difference was observed in older patients. The correlation coefficient between the telomerase activity and telomere length of PBMC in SLE patients was not significant. Abnormalities in the telomerase activity and telomere length observed in SLE patients are considered to be important findings for evaluation of the pathology of SLE.
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ABSTRACT: Telomeres are specialized nucleoproteic structures that cap and protect the ends of chromosomes. They can be elongated by the telomerase enzyme, but in telomerase negative cells, telomeres shorten after each cellular division because of the end replicating problem. This phenomenon leads ultimately to cellular senescence, conferring to the telomeres a role of biological clock. Oxidative stress, inflammation and increased cell renewal are supplementary environmental factors that accelerate age-related telomere shortening. Similar to other types of DNA damage, very short/dysfunctional telomeres activate a DNA response pathway leading to different outcomes: DNA repair, cell senescence or apoptosis. During the last 10 years, studies on the telomere/telomerase system in autoimmune and/or systemic immune-mediated diseases have revealed its involvement in relevant physiopathological processes. Here, we present a literature review of telomere and telomerase homeostasis in systemic inflammatory diseases including systemic lupus erythematosus, rheumatoid arthritis and granulomatous diseases. The available data indicate that both telomerase activity and telomere length are modified in various systemic immune-mediated diseases and appear to be connected with premature immunosenescence. Studies on the telomere/telomerase system open new research avenues for the basic understanding and for therapeutic approaches of these pathologies.Autoimmunity reviews 05/2010; 9(10):646-51. · 6.37 Impact Factor
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ABSTRACT: Primary biliary cirrhosis (PBC) is a cholestatic liver disease characterised by the autoimmune destruction of the small intrahepatic bile ducts. The disease has an unpredictable clinical course, but may progress to fibrosis and cirrhosis. Although medical treatment with urseodeoxycholic acid is largely successful, some patients may progress to liver failure requiring liver transplantation. PBC is characterised by the presence of disease specific anti-mitochondrial (AMA) antibodies, which are pathognomonic for PBC development. The disease demonstrates an overwhelming female preponderance and virtually all women with PBC present in middle age. The reasons for this are unknown; however several environmental and immunological factors may be involved. As the immune systems ages, it become less self tolerant, and mounts a weaker response to pathogens, possibly leading to cross reactivity or molecular mimicry. Some individuals display immunological changes which encourage the development of autoimmune disease. Risk factors implicated in PBC include recurrent urinary tract infection in females, as well as an increased prevalence of reproductive complications. These risk factors may work in concert with and possibly even accelerate, immune system ageing, contributing to PBC development. This review will examine the changes that occur in the immune system with ageing, paying particular attention to those changes which contribute to the development of autoimmune disease with increasing age. The review also discusses risk factors which may account for the increased female predominance of PBC, such as recurrent UTI and oestrogens.Immunity & Ageing 12/2011; 8(1):12.