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Telomere length analysis in monocytes and lymphocytes from patients with systemic lupus erythematosus using multi-color flow-FISH
F. Beier
Division of Hematology, Oncology and Immunology, University of Tubingen, Germany
S. Balabanov
Division of Hematology, Oncology and Immunology, University of Tubingen, Germany, Department of Hematology and Oncology, University Hospital Eppendorf, Hamburg, Germany
C.C. Amberger
Division of Hematology, Oncology and Immunology, University of Tubingen, Germany
U. Hartmann
Division of Hematology, Oncology and Immunology, University of Tubingen, Germany, Department of Pharmacology, University of Tubingen, Germany
K. Manger
Department of Rheumatology, University of Erlangen, Germany
K. Dietz
Department of Medical Biometry, University of Tubingen, Germany
I. Kötter
Division of Hematology, Oncology and Immunology, University of Tubingen, Germany
T.H. Brummendorf
Division of Hematology, Oncology and Immunology, University of Tubingen, Germany, Department of Hematology and Oncology, University Hospital Eppendorf, Hamburg, Germany, t.bruemmendorf{at}uke.uni-hamburg.de
In order to analyse telomere length in subsets of human peripheral blood lymphocytes and monocytes, we modified a recently developed multicolor flow- fluorescent in situ hybridization (FISH) methodology that combines flow-FISH and antibody staining for cell surface antigens. We analysed telomere length of peripheral blood mononuclear cells in a group of 22 patients with systemic lupus erythematosus (SLE) and 20 age-matched healthy donors. We found that neither CD4+, CD8+, CD19+ cells nor CD14+ monocytes have significantly shorter telomeres compared with their healthy counterparts. On the basis of these findings, we then used monocyte telomere length as internal reference in order to control for intra-individual variability in telomere length. By using this approach, we could demonstrate significant telomere shortening in all three lymphocyte subsets (in all cases P < 0.05) compared with monocytes. However, these differences did not vary significantly between SLE patients and controls. In summary, telomere lengths in subpopulations of hematopoietic cells can be monitored in patients with SLE using multicolor flow-FISH. While confirming data by other groups on telomere length in lymphocyte subpopulations, our data argue against an increased proliferation rate of peripheral blood monocytes reflected by accelerated telomere shortening in patients with SLE. Lupus (2007) 16, 955—962.
Key Words: flow-FISH monocyte systemic lupus erythematosus telomere telomerase
References
- Blackburn EH Structure and function of telomeres. Nature 1991; 350: 569—573.[CrossRef][Medline]
[Order article via Infotrieve]
- Hayflick L. Aging under glass. Mutat Res 1991; 256: 69—80.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Levy MZ, Allsopp RC, Futcher AB, Greider CW, Harley CB Telomere end-replication problem and cell aging. J Mol Biol 1992; 225: 951—960.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Allsopp RC, Vaziri H., Patterson C. et al. Telomere length predicts replicative capacity of human fibroblasts. Proc Natl Acad Sci USA 1992; 89: 10114—10118.[Abstract/Free Full Text]
- Brummendorf TH, Balabanov S. Telomere length dynamics in normal hematopoiesis and in disease states characterized by increased stem cell turnover. Leukemia 2006; 20: 1706—1716.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Mills JA Systemic lupus erythematosus. N Engl J Med 1994; 330: 1871—1879.[Free Full Text]
- Crispin JC, cocer-Varela J. Interleukin-2 and systemic lupus erythematosus — fifteen years later. Lupus 1998; 7: 214—222.[Abstract/Free Full Text]
- Lipsky PE Systemic lupus erythematosus: an autoimmune disease of B cell hyperactivity. Nat Immunol 2001; 2: 764—766.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Rus V., Via CS Telomeres, telomerase, and lupus: the long and short of it. Clin Immunol 2001; 99: 195—197.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Blanco P., Palucka AK, Gill M., Pascual V., Banchereau J. Induction of dendritic cell differentiation by IFN-alpha in systemic lupus erythematosus. Science 2001; 294: 1540—1543.[Abstract/Free Full Text]
- Palucka AK, Banchereau J., Blanco P., Pascual V. The interplay of dendritic cell subsets in systemic lupus erythematosus. Immunol Cell Biol 2002; 80: 484—488.[CrossRef][Medline]
[Order article via Infotrieve]
- Schonland SO, Lopez C., Widmann T. et al. Premature telomeric loss in rheumatoid arthritis is genetically determined and involves both myeloid and lymphoid cell lineages. Proc Natl Acad Sci USA 2003; 100: 13471—13476.[Abstract/Free Full Text]
- Steer SE, Williams FM, Kato B. et al. Reduced telomere length in rheumatoid arthritis is independent of disease activity and duration. Ann Rheum Dis 2007; 66: 476—480.[Abstract/Free Full Text]
- Wu K., Higashi N., Hansen ER et al. Telomerase activity is increased and telomere length shortened in T cells from blood of patients with atopic dermatitis and psoriasis. J Immunol 2000; 165: 4742—4747.[Abstract/Free Full Text]
- Fritsch RD, Shen X., Illei GG et al. Abnormal differentiation of memory T cells in systemic lupus erythematosus. Arthritis Rheum 2006; 54: 2184—2197.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Honda M., Mengesha E., Albano S. et al. Telomere shortening and decreased replicative potential, contrasted by continued proliferation of telomerase-positive CD8 + CD28(lo) T cells in patients with systemic lupus erythematosus. Clin Immunol 2001; 99: 211—221.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Klapper W., Moosig F., Sotnikova A. et al. Telomerase activity in B and T lymphocytes of patients with systemic lupus erythematosus. Ann Rheum Dis 2004; 63: 1681—1683.[Abstract/Free Full Text]
- Kurosaka D., Yasuda J., Yoshida K. et al. Telomerase activity and telomere length of peripheral blood mononuclear cells in SLE patients. Lupus 2003; 12: 591—599.[Abstract/Free Full Text]
- Kurosaka D., Yasuda J., Yoshida K. et al. Abnormal telomerase activity and telomere length in T and B cells from patients with systemic lupus erythematosus. J Rheumatol 2006; 33: 1102—1107.[Abstract/Free Full Text]
- Wu CH, Hsieh SC, Li KJ, Lu MC, Yu CL Premature telomere shortening in polymorphonuclear neutrophils from patients with systemic lupus erythematosus is related to the lupus disease activity. Lupus 2007; 16: 265—272.[Abstract/Free Full Text]
- Rufer N., Dragowska W., Thornbury G., Roosnek E., Lansdorp PM Telomere length dynamics in human lymphocyte subpopulations measured by flow cytometry. Nat Biotechnol 1998; 16: 743—747.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Baerlocher GM, Mak J., Tien T., Lansdorp PM Telomere length measurement by fluorescence in situ hybridization and flow cytometry: tips and pitfalls. Cytometry 2002; 47: 89—99.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Baerlocher GM, Lansdorp PM Telomere length measurements using fluorescence in situ hybridization and flow cytometry. Methods Cell Biol 2004; 75: 719—750.[Web of Science][Medline]
[Order article via Infotrieve]
- Bartolovic K., Balabanov S., Berner B. et al. Clonal heterogeneity in growth kinetics of CD34+. Stem Cells 2005; 23: 946—957.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Batliwalla FM, Damle RN, Metz C., Chiorazzi N., Gregersen PK Simultaneous flow cytometric analysis of cell surface markers and telomere length: analysis of human tonsilar B cells. J Immunol Methods 2001; 247: 103—109.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Beier F., Balabanov S., Buckley T. et al. Accelerated telomere shortening in glycosylphosphatidylinositol (GPI)-negative compared with GPI-positive granulocytes from patients with paroxysmal nocturnal hemoglobinuria (PNH) detected by proaerolysin flow-FISH. Blood 2005; 106: 531—533.[Abstract/Free Full Text]
- Hartmann U., Brummendorf TH, Balabanov S. et al. Telomere length and hTERT expression in patients with acute myeloid leukemia correlates with chromosomal abnormalities. Haematologica 2005; 90: 307—316.[Abstract/Free Full Text]
- Rufer N., Brummendorf TH, Kolvraa S. et al. Telomere fluorescence measurements in granulocytes and T lymphocyte subsets point to a high turnover of hematopoietic stem cells and memory T cells in early childhood. J Exp Med 1999; 190: 157—167.[Abstract/Free Full Text]
- Harley CB, Vaziri H., Counter CM, Allsopp RC The telomere hypothesis of cellular aging. Exp Gerontol 1992; 27: 375—382.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Blasco MA, Lee HW, Hande MP et al. Telomere shortening and tumor formation by mouse cells lacking telomerase RNA. Cell 1997; 91: 25—34.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Knight SW, Heiss NS, Vulliamy TJ et al. X-linked dyskeratosis congenita is predominantly caused by missense mutations in the DKC1 gene. Am J Hum Genet 1999; 65: 50—58.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Vulliamy T., Marrone A., Goldman F. et al. The RNA component of telomerase is mutated in autosomal dominant dyskeratosis congenita. Nature 2001; 413: 432—435.[CrossRef][Medline]
[Order article via Infotrieve]
- Rufer N., Brummendorf TH, Chapuis B. et al. Accelerated telomere shortening in hematological lineages is limited to the first year following stem cell transplantation. Blood 2001; 97: 575—577.[Abstract/Free Full Text]
- Andrew T., Aviv A., Falchi M. et al. Mapping genetic loci that determine leukocyte telomere length in a large sample of unselected female sibling pairs. Am J Hum Genet 2006; 78: 480—486.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Slagboom PE, Droog S., Boomsma DI Genetic determination of telomere size in humans: a twin study of three age groups. Am J Hum Genet 1994; 55: 876—882.[Web of Science][Medline]
[Order article via Infotrieve]
- Lansdorp PM Stress, social rank and leukocyte telomere length. Aging Cell 2006; 5: 583—584.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Cherkas LF, Aviv A., Valdes AM et al. The effects of social status on biological aging as measured by white-blood-cell telomere length. Aging Cell 2006; 5: 361—365.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Valdes AM, Andrew T., Gardner JP et al. Obesity, cigarette smoking, and telomere length in women. Lancet 2005; 366: 662—664.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Brummendorf TH, Holyoake TL, Rufer N. et al. Prognostic implications of differences in telomere length between normal and malignant cells from patients with chronic myeloid leukemia measured by flow cytometry. Blood 2000; 95: 1883—1890.[Abstract/Free Full Text]
- Drummond M., Lennard A., Brummendorf T., Holyoake T. Telomere shortening correlates with prognostic score at diagnosis and proceeds rapidly during progression of chronic myeloid leukemia. Leuk Lymphoma 2004; 45: 1775—1781.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Fritsch RD, Shen X., Sims GP et al. Stepwise differentiation of CD4 memory T cells defined by expression of CCR7 and CD27. J Immunol 2005; 175: 6489—6497.[Abstract/Free Full Text]
Lupus, Vol. 16, No. 12,
955-962 (2007)
DOI: 10.1177/0961203307084299

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