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Blood, 15 January 2005, Vol. 105, No. 2, pp. 682-688. Prepublished online as a Blood First Edition Paper on July 6, 2004; DOI 10.1182/blood-2004-04-1673. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-04-1673v1 105/2/682    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Knudson, M. Articles by Goldman, F. Search for Related Content PubMed PubMed Citation Articles by Knudson, M. Articles by Goldman, F. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Association of immune abnormalities with telomere shortening in autosomal-dominant dyskeratosis congenita Matt Knudson, Shashikant Kulkarni, Zuhair K. Ballas, Monica Bessler, and Frederick Goldman From the Department of Pediatrics, University of Iowa Hospitals and Clinics, Iowa City, IA; Department of Internal Medicine, Washington University School of Medicine, St Louis, MO; and Department of Internal Medicine, University of Iowa Hospitals and Clinics and the Iowa City Veterans Affairs Medical Center, Iowa City, IA. Dyskeratosis congenita (DC) is an inherited bone marrow failure disorder characterized by abnormal skin pigmentation and nail dystrophy. We have recently described, in 10 members of a large 3-generation family, an autosomal-dominant form of DC (AD DC) that is due to a mutation in the gene-encoding human telomerase RNA (TERC), resulting in telomere shortening. In studying the immunologic consequences of TERC mutations, severe B lymphopenia and decreased immunoglobulin M (IgM) levels were noted. T cells were found to overexpress senescent markers, including CD57 and Fas receptor, and were moderately reduced in cell number. To determine whether these in vivo findings were related to cellular replicative defects, short-term cultures of AD DC lymphocytes were established to measure proliferation, mitoses, and apoptosis. AD DC lymphocytes displayed a markedly reduced proliferative capacity and increased basal apoptotic rate. Finally, telomere shortening was most prominent in third-generation subjects, and there appeared to be a correlation between telomere length and in vivo and in vitro immune findings. In summary, the observed lymphopenia and hypogammaglobulinemia in AD DC is likely a consequence of replicative failure and premature senescence of lymphocytes, supporting a role of telomerase activity in immune homeostasis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. D. Goldman, G. Aubert, A. J. Klingelhutz, M. Hills, S. R. Cooper, W. S. Hamilton, A. J. Schlueter, K. Lambie, C. J. Eaves, and P. M. Lansdorp Characterization of primitive hematopoietic cells from patients with dyskeratosis congenita Blood, May 1, 2008; 111(9): 4523 - 4531. [Abstract] [Full Text] [PDF] J. M. Liu and S. R. Ellis Ribosomes and marrow failure: coincidental association or molecular paradigm? Blood, June 15, 2006; 107(12): 4583 - 4588. [Abstract] [Full Text] [PDF] F. Goldman, R. Bouarich, S. Kulkarni, S. Freeman, H.-Y. Du, L. Harrington, P. J. Mason, A. Londono-Vallejo, and M. Bessler The effect of TERC haploinsufficiency on the inheritance of telomere length PNAS, November 22, 2005; 102(47): 17119 - 17124. [Abstract] [Full Text] [PDF]

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