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Blood, 15 February 2004, Vol. 103, No. 4, pp. 1244-1252. Prepublished online as a Blood First Edition Paper on October 23, 2003; DOI 10.1182/blood-2003-06-2171. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-06-2171v1 103/4/1244    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 Katano, H. Articles by Cohen, J. I. Search for Related Content PubMed PubMed Citation Articles by Katano, H. Articles by Cohen, J. I. Related Collections Immunobiology Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS Chronic active Epstein-Barr virus infection associated with mutations in perforin that impair its maturation Harutaka Katano, Mir A. Ali, Andriani C. Patera, Marta Catalfamo, Elaine S. Jaffe, Hiroshi Kimura, Janet K. Dale, Stephen E. Straus, and Jeffrey I. Cohen From the Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH); the Experimental Immunology Branch and the Laboratory of Pathology, National Cancer Institute, NIH, Bethesda, MD; and the Department of Pediatrics, Nagoya University Graduate School of Medicine, Aichi, Japan. Chronic active Epstein-Barr virus infection (CAEBV) is a rare disease in which previously healthy persons develop severe, life-threatening illness. Mutations in the perforin gene have been found in familial hemophagocytic lymphohistiocytosis, which shares some features with CAEBV. We studied a patient who died at age 18, 10 years after the onset of CAEBV. The patient had high titers of antibodies to EBV, EBV RNA in lymph nodes, T-cell lymphoproliferative disease, and hemophagocytic lymphohistiocytosis. DNA sequencing showed novel mutations in both alleles of the perforin gene that resulted in amino acid changes in the protein. The quantity of the native form of perforin from the patient's stimulated peripheral blood mononuclear cells (PBMCs) was extremely low and immunoblotting showed accumulation of an uncleaved precursor form of perforin. Stimulated PBMCs from the patient were defective for Fas-independent cytotoxicity. These data imply that mutations in this patient resulted in reduced perforin-mediated cytotoxicity by his lymphocytes. This is the first case in which perforin mutations have been shown to result in accumulation of the uncleaved, immature form of perforin. Mutations in the perforin gene are associated with some cases of CAEBV with hemophagocytic lymphohistiocytosis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. I. Cohen, H. Kimura, S. Nakamura, Y.-H. Ko, and E. S. Jaffe Epstein-Barr virus-associated lymphoproliferative disease in non-immunocompromised hosts: a status report and summary of an international meeting, 8-9 September 2008 Ann. Onc., September 1, 2009; 20(9): 1472 - 1482. [Abstract] [Full Text] [PDF] J. L. Meade, E. B. Wilson, T. D. Holmes, E. A. de Wynter, P. Brett, L. Straszynski, P. A. S. Ballard, J. A. Trapani, M. F. McDermott, and G. P. Cook Proteolytic Activation of the Cytotoxic Phenotype during Human NK Cell Development J. Immunol., July 15, 2009; 183(2): 803 - 813. [Abstract] [Full Text] [PDF] J. Chia, K. P. Yeo, J. C. Whisstock, M. A. Dunstone, J. A. Trapani, and I. Voskoboinik Temperature sensitivity of human perforin mutants unmasks subtotal loss of cytotoxicity, delayed FHL, and a predisposition to cancer PNAS, June 16, 2009; 106(24): 9809 - 9814. [Abstract] [Full Text] [PDF] R. Urrea Moreno, J. Gil, C. Rodriguez-Sainz, E. Cela, V. LaFay, B. Oloizia, A. B. Herr, J. Sumegi, M. B. Jordan, and K. A. Risma Functional assessment of perforin C2 domain mutations illustrates the critical role for calcium-dependent lipid binding in perforin cytotoxic function Blood, January 8, 2009; 113(2): 338 - 346. [Abstract] [Full Text] [PDF] H. Williams and D. H. Crawford Epstein-Barr virus: the impact of scientific advances on clinical practice Blood, February 1, 2006; 107(3): 862 - 869. [Abstract] [Full Text] [PDF] C. Trambas, F. Gallo, D. Pende, S. Marcenaro, L. Moretta, C. De Fusco, A. Santoro, L. Notarangelo, M. Arico, and G. M. Griffiths A single amino acid change, A91V, leads to conformational changes that can impair processing to the active form of perforin Blood, August 1, 2005; 106(3): 932 - 937. [Abstract] [Full Text] [PDF] J. Loh, D. A. Thomas, P. A. Revell, T. J. Ley, and H. W. Virgin IV Granzymes and Caspase 3 Play Important Roles in Control of Gammaherpesvirus Latency J. Virol., November 15, 2004; 78(22): 12519 - 12528. [Abstract] [Full Text] [PDF] N. J. Karandikar, S. H. Kroft, S. Yegappan, B. B. Rogers, V. M. Aquino, K.-M. Lee, V. Kumar, F. J. Guenaga, E. S. Jaffe, D. C. Douek, et al. Unusual immunophenotype of CD8+ T cells in familial hemophagocytic lymphohistiocytosis Blood, October 1, 2004; 104(7): 2007 - 2009. [Abstract] [Full Text] [PDF]

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