Abstract
Telomerase is a reverse transcriptase enzyme contributing to the maintenance of the telomeric structure by adding telomere repeat sequences to chromosomal ends, thus compensating for its shortening. Telomerase activity which is common in cancers and human germ line tissue, may also be increased, although to a lesser extent, in systemic autoimmune diseases. We aimed to evaluate telomerase activity in a group of Turkish patients with various connective tissue diseases. In this cross sectional study, 19 patients with systemic sclerosis (SSc), 15 with systemic lupus erythematosus (SLE), 10 with rheumatoid arthritis (RA) and 14 with primary Sjögren’s syndrome (pSjS) were studied. As the control group, 29 healthy subjects were also included. Human telomerase-specific reverse transcriptase (hTERT) was measured in peripheral blood lymphocytes, using online real-time reverse-transcriptase polymerase chain reaction (PCR). We also investigated if hTERT values in each patient group were correlated with clinical parameters and disease activity. Highest hTERT values were observed in RA group (21.24 ± 28.54), followed by SLE (13.38 ± 26.05) and pSjS (11.73 ± 10.59) groups. Only hTERT values in RA group was significantly higher than the healthy control group (7.62 ± 4.21) (p < 0.05). Interestingly, hTERT values in SSc were very low (2.09 ± 3.18), even less than the healthy control group. In consistent with previous studies, telomerase activity was increased in SLE and RA. Very low telomerase activity in SSc group was rather surprising. Since existing telomerase data in SSc was limited and telomere shortening was previously reported in SSc, our finding of low telomerase activity in SSc group deserves relevant discussion and further studies.
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Goronzy JJ, Fujii H, Weyand CM (2006) Telomeres, immune aging and autoimmunity. Exp Gerontol 41:246–251
Zakian VA (1995) Telomeres: beginning to understand the end. Science 270:1601–1607
Shay JW, Bacchetti S (1997) A survey of telomerase activity in human cancer. Eur J Cancer 33:787–791
Kim NW, Piatyszek MA, Prowse KR et al. (1994) Specific association of human telomerase activity with immortal cells and cancer. Science 266:2011–2015
Hiyama K, Hirai Y, Kyoizumi S et al. (1995) Activation of telomerase in human lymphocytes and hematopoietic progenitor cells. J Immunol 155:3711–3715
Weng N, Levine BL, June CH, Hodes RJ (1997) Regulation of telomerase RNA template expression in human T lymphocyte development and activation. J Immunol 158:3215–3220
Weng NP, Palmer LD, Levine BL, Lane HC, June CH, Hodes RJ (1997) Tales of tails: regulation of telomere length and telomerase activity during lymphocyte development, differentiation, activation, and aging. Immunol Rev 160:43–54
Iwama H, Ohyashiki K, Ohyashiki JH et al. (1998) Telomeric length and telomerase activity vary with age in peripheral blood cells obtained from normal individuals. Hum Genet 102:397–402
Katayama Y, Kohriyama K (2001) Telomerase activity in peripheral blood mononuclear cells of systemic connective tissue diseases. J Rheumatol 28:288–291
Kurosaka D, Ozawa Y, Yasuda J et al (2001) Telomerase activity in peripheral blood mononuclear cells from patients with SLE. Ann Rheum Dis 60:1158–1159
Klapper W, Moosig F, Sotnikova A, Qian W, Schroder JO, Parwaresch R (2004) Telomerase activity in B and T lymphocytes of patients with systemic lupus erythematosus. Ann Rheum Dis 63:1681–1683
Kurosaka D, Yasuda J, Yoshida K et al. (2003) Telomerase activity and telomere length of peripheral blood mononuclear cells in SLE patients. Lupus 12:591–599
Klapper W, Moosig F, Sotnikova A, Qian W, Schroder JO, Parwaresch R (2004) Telomerase activity in B and T lymphocytes of patients with systemic lupus erythematosus. Ann Rheum Dis 63:1681–1683
Kurosaka D, Yasuda J, Yoshida K et al. (2006) Abnormal telomerase activity and telomere length in T and B cells from patients with systemic lupus erythematosus. J Rheumatol 33:1102–1107
Thewissen M, Linsen L, Geusens P, Raus J, Stinissen P (2005) Impaired activation-induced telomerase activity in PBMC of early but not chronic rheumatoid arthritis patients. Immunol Lett 100:205–210
Tsumuki H, Hasunuma T, Kobata T, Kato T, Uchida A, Nishioka K (2000) Basic FGF-induced activation of telomerase in rheumatoid synoviocytes. Rheumatol Int 19:123–128
Yamanishi Y, Hiyama K, Maeda H, Ishioka S, Murakami T, Hiyama E, Kurose Y, Shay JW, Yamakido M (1998) Telomerase activity in rheumatoid synovium correlates with the mononuclear cell infiltration level and disease aggressiveness of rheumatoid arthritis. J Rheumatol 25(2):214–220
Ohtsuka T, Yamakage A, Yamazaki S (2002) The polymorphism of telomerase RNA component gene in patients with systemic sclerosis. Br J Dermatol 147:250–254
Artlett CM, Black CM, Briggs DC, Stevens CO, Welsh KI (1996) Telomere reduction in scleroderma patients: a possible cause for chromosomal instability. Br J Rheumatol 35:732–737
Kim NW, Piatyszek MA, Prowse KR, Harley CB, West MD, Ho PL, Coviello GM, Wright WE, Weinrich SL, Shay JW (1994) Specific association of human telomerase activity with immortal cells and cancer. Science 266:2011–2015
Longchampt E, Lebret T, Molinie, Bieche I, Botto H, Lidereau R (2003) Detection of telomerase status by semiquantitative and in situ assays, and by real-time reverse transcription polymerase chain reaction (telomerase reverse transcriptase) assay in bladder carcinomas. BJU Int 91:567–572
Ernst A, Okkels H, Grove A et al. (2006) Telomerase activity determined by conventional telomeric repeat amplification protocol and reverse transcriptase-polymerase chain reaction assay in ovarian lesions: a comparison of assays. Scand J Clin Lab Invest 66:287–297
Jakupciak JP, Wang W, Barker PE, Srivastava S, Atha DH (2004) Analytical validation of telomerase activity for cancer early detection TRAP/PCR-CE and hTERT mRNA quantification assay for high-throughput screening of tumor cells. J Mol Diagn 6:157–165
Medsger TA Jr, Steen VD (1996) Classification, prognosis. In: Clements PJ, Furst DE (eds) Systemic sclerosis. Williams & Wilkins, Baltimore, pp 51–64
Tan EM, Cohen AS, Fries JF et al. (1991) The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 34:945–950
Arnett FC, Edworthy SM, Bloch DA et al. (1988) The American rheumatism association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31:315–324
Vitali C, Bombardieri S, Jonsson R et al. (2002) Classification criteria for Sjogren’s syndrome: a revised version of the European criteria proposed by the American–European consensus group. Ann Rheum Dis 61:554–558
Kyo S, Takakura M, Kanaya T et al. (1999) Estrogen activates telomerase. Cancer Res 59:5917–5921
Son NH, Murray S, Yanovski J, Hodes RJ, Weng N (2000) Lineage-specific telomere shortening and unaltered capacity for telomerase expression in human T and B lymphocytes with age. J Immunol 165:1191–1196
Yudoh K, Matsuno H, Nezuka T, Kimura T (1999) Different mechanisms of synovial hyperplasia in rheumatoid arthritis and pigmented villonodular synovitis: the role of telomerase activity in synovial proliferation. Arthritis Rheum 42:669–677
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Tarhan, F., Vural, F., Kosova, B. et al. Telomerase activity in connective tissue diseases: elevated in rheumatoid arthritis, but markedly decreased in systemic sclerosis . Rheumatol Int 28, 579–583 (2008). https://doi.org/10.1007/s00296-007-0472-9
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DOI: https://doi.org/10.1007/s00296-007-0472-9