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Blood, 15 November 2008, Vol. 112, No. 10, pp. 4090-4097. Prepublished online as a Blood First Edition Paper on August 26, 2008; DOI 10.1182/blood-2008-04-153361. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-04-153361v1 112/10/4090    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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Speckmann, C. Articles by Ehl, S. Search for Related Content PubMed PubMed Citation Articles by Speckmann, C. Articles by Ehl, S. Related Collections Immunobiology Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Clinical and immunologic consequences of a somatic reversion in a patient with X-linked severe combined immunodeficiency Carsten Speckmann1, Ulrich Pannicke2, Elisabeth Wiech3, Klaus Schwarz2, Paul Fisch3, Wilhelm Friedrich4, Tim Niehues5, Kimberly Gilmour6, Karin Buiting7, Michael Schlesier8, Hermann Eibel8, Jan Rohr1, Andrea Superti-Furga1, Ute Groß-Wieltsch9, and Stephan Ehl1 1 Center for Paediatrics and Adolescent Medicine, University of Freiburg, Freiburg, Germany; 2 Institute for Transfusion Medicine, University Hospital Ulm and Institute for Clinical Transfusion Medicine and Immunogenetics, Ulm, Germany; 3 Institute for Pathology, University of Freiburg, Freiburg, Germany; 4 Department of Paediatrics and Adolescent Medicine, University Hospital, Ulm, Germany; 5 Helios Kliniken Krefeld, Krefeld, Germany; 6 Molecular Immunology Unit, Institute of Child Health, University College London, London, United Kingdom; 7 Institute for Human Genetics, University Hospital Essen, Essen, Germany; 8 Medical Center, Department of Rheumatology and Immunology, University of Freiburg, Freiburg, Germany; and 9 Department of Haematology and Oncology, Olgaspital, Stuttgart, Germany X-linked severe combined immunodeficiency is a life-threatening disorder caused by mutations in the gene encoding the interleukin-2 receptor gamma chain (IL2RG). Hypomorphic mutations and reversion of mutations in subpopulations of cells can result in variant clinical phenotypes, making diagnosis and treatment difficult. We describe a 5-year-old boy with mild susceptibility to infection who was investigated for a mutation in IL2RG due to persistent natural killer (NK)– and T-cell lymphopenia. A functionally relevant novel T466C point mutation was found in B, NK, and epithelial cells, whereas /β and / T cells showed the normal gene sequence, suggesting reversion of the mutation in a common T-cell precursor. This genetic correction in T cells resulted in a diverse T-cell repertoire and significant immunity despite failure to produce specific antibodies linked to an intrinsic defect of mutant B cells. These observations confirm the potential of revertant T-cell precursors to reconstitute immune function, but questions remain on the longevity of revertant cells implicating the need for careful follow up and early consideration of hematopoietic stem cell transplantation (HSCT). CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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