Association of increased telomere lengths in limited scleroderma, with a lack of age-related telomere erosion

Abstract

Objectives: Telomere erosion, a feature of biological ageing, is implicated in a wide range of diseases. Its impact on autoimmune diseases remains unclear although autoantibodies against many telomere nucleoprotein components are prevalent in these diseases. We aimed to assess if telomere biology was abnormal in a cohort of patients with limited cutaneous systemic sclerosis (lcSSc). Methods: Telomere lengths in peripheral blood leucocytes (PBL) were determined using Southern blotting methods in a cohort of lcSSc subjects (n = 43; age range 37-80 years) and a control population (n = 107; age range 21-65 years). Results: Telomere lengths in lcSSc subjects were longer than controls (p,0.001), did not show age-related telomere erosion and differed significantly from agematched controls only after 50 years of age (p,0.001).Conclusions: This is the first report of maintenance of telomere lengths in an autoimmune disease state. These data indicate aberrant telomere biology and irregular biological ageing from the fifth decade of life. These findings provide insight into compromised DNA damage repair in lcSSc. Whether these observations indicate a causal or consequential relationship requires further investigation. This in turn, may provide potential novel targets for therapeutic intervention.

Telomere dysfunction in peripheral blood lymphocytes from patients with primary sclerosing cholangitis and inflammatory bowel disease

“…Thus, many studies have observed that accelerated telomere loss is a common feature of systemic autoimmune disease, such as systemic lupus erythematosus or rheumatoid arthritis [37], and local or systemic fibrotic conditions, such as scleroderma [38], idiopathic pulmonary fibrosis [39] and cirrhosis [32,36]. The combination of inflammatory, autoimmune and fibrotic processes in PSC, increases the potential for a telomeretelomerase system dysfunction, as found in our study.…”

Telomere Dysfunction in Nonalcoholic Fatty Liver Disease and Cryptogenic Cirrhosis

“…First, the presence of underlying metabolic disorders mentioned above. Second, accelerated telomere loss has been implicated in other local or systemic fibrotic conditions, such as scleroderma [MacIntyre et al, 2008] and idiopathic pulmonary fibrosis [Armanios et al, 2007]. Cirrhosis from any etiology, including CC, is another local fibrotic disease with systemic implications and, thus, is expected to cause telomere shortening, as indeed was demonstrated previously [Wiemann et al, 2002;Chaiteerakij and Roberts, 2011].…”

Patients with gout have short telomeres compared with healthy participants: association of telomere length with flare frequency and cardiovascular disease in gout

“…In various tissues and cell-subtypes, accelerated cell turnover is inversely associated with replicative senescence. In disorders involving accelerated oxidative injury and chronic immune system activation as the main manifestation, such as systemic lupus erythematosus,33 rheumatoid arthritis32 and systemic sclerosis,34 enhanced cell turnover and telomere erosion has been extensively described. Furthermore, we observed no significant TL difference in treated patients with gout compared with patients without treatment.…”