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Blood, 15 August 2006, Vol. 108, No. 4, pp. 1306-1312. Prepublished online as a Blood First Edition Paper on April 20, 2006; DOI 10.1182/blood-2006-04-015776. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-04-015776v1 108/4/1306    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 Del-Rey, M. Articles by Allende, L. M. Search for Related Content PubMed PubMed Citation Articles by Del-Rey, M. Articles by Allende, L. M. Related Collections Immunobiology Neoplasia Apoptosis Clinical Trials and Observations Related Letter in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY A homozygous Fas ligand gene mutation in a patient causes a new type of autoimmune lymphoproliferative syndrome Manuel Del-Rey, Jesus Ruiz-Contreras, Alberto Bosque, Sara Calleja, Jose Gomez-Rial, Ernesto Roldan, Pablo Morales, Antonio Serrano, Alberto Anel, Estela Paz-Artal, and Luis M. Allende From the Servicio de Inmunología and Unidad de Inmunodeficiencias, Hospital Universitario 12 de Octubre, Madrid; Departamento de Bioquímica, Biología Molecular y Celular, Universidad de Zaragoza; and Servicio de Inmunología, Hospital Ramón y Cajal, Madrid, Spain. Autoimmune lymphoproliferative syndrome (ALPS) is characterized by lymphoproliferation and autoimmune clinical manifestations and is generally caused by defective Fas-mediated apoptosis. This report describes the first homozygous FASL gene mutation in a woman with clinical and immunologic features of ALPS. T-cell blasts from the patient did not induce FasL-mediated apoptosis on Fas-transfected murine L1210 or on Jurkat cells, and activation-induced cell death was impaired. Furthermore, Fas-dependent cytotoxicity was drastically reduced in COS cells transfected with the mutant FasL. In addition, FasL expression on T-cell blasts from the patient was similar to that observed in a healthy control, despite its bearing the high-producer genotype –844C/C in the FASL promoter. Sequencing of the patient's FASL gene revealed a new mutation in exon 4 (A247E). The location of A247E in the FasL extracellular domain and the conservation of the protein sequence of that region recorded in 8 species different from humans support the essential role of FasL COOH terminal domain in Fas/FasL binding. These findings provide evidence that inherited nonlethal FASL abnormalities cause an uncommon apoptosis defect producing lymphoproliferative disease, and they highlight the need for a review of the current ALPS classification to include a new ALPS type Ic subgroup. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Letter in Blood Online: Analysis of the CD95 ligand gene in 20 children with autoimmune lymphoproliferative syndrome (ALPS) Eva Pauly, Benedikt Fritzsching, Markus Dechant, Joerg Fellenberg, Christian Gerold Scheuerpflug, Klaus-Michael Debatin, Estela Paz-Artal, Manuel Del-Rey, Sara Calleja, Pablo Morales, Antonio Serrano, and Luis M. Allende Blood 2006 108: 3622-3623. [Full Text] [PDF] This article has been cited by other articles: A. Bosque, J. I. Aguilo, M. del Rey, E. Paz-Artal, L. M. Allende, J. Naval, and A. Anel Cell cycle regulation by FasL and Apo2L/TRAIL in human T-cell blasts. Implications for autoimmune lymphoproliferative syndromes J. Leukoc. Biol., August 1, 2008; 84(2): 488 - 498. [Abstract] [Full Text] [PDF] V. Mateo, M. Menager, G. de Saint-Basile, M.-C. Stolzenberg, B. Roquelaure, N. Andre, B. Florkin, F. le Deist, C. Picard, A. Fischer, et al. Perforin-dependent apoptosis functionally compensates Fas deficiency in activation-induced cell death of human T lymphocytes Blood, December 15, 2007; 110(13): 4285 - 4292. [Abstract] [Full Text] [PDF] A. Bosque, J. I. Aguilo, M. A. Alava, E. Paz-Artal, J. Naval, L. M. Allende, and A. Anel The induction of Bim expression in human T-cell blasts is dependent on nonapoptotic Fas/CD95 signaling Blood, February 15, 2007; 109(4): 1627 - 1635. [Abstract] [Full Text] [PDF] J-M Andre, R Cimaz, B Ranchin, C Galambrun, Y Bertrand, R Bouvier, F Rieux-Laucat, M-C Trescol-Biemont, P Cochat, and N Bonnefoy-Berard Overexpression of the antiapoptotic gene Bfl-1 in B cells from patients with familial systemic lupus erythematosus Lupus, February 1, 2007; 16(2): 95 - 100. [Abstract] [PDF] E. Pauly, B. Fritzsching, M. Dechant, J. Fellenberg, C. G. Scheuerpflug, K.-M. Debatin, E. Paz-Artal, M. Del-Rey, S. Calleja, P. Morales, et al. Analysis of the CD95 ligand gene in 20 children with autoimmune lymphoproliferative syndrome (ALPS). Blood, November 15, 2006; 108(10): 3622 - 3623. [Full Text] [PDF]

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