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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 (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 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 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 Related Letter in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 7, 2006 Accepted April 7, 2006 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* Servicio de Inmunologia, Hospital Universitario 12 de Octubre, Madrid, Spain Unidad de Inmunodeficiencias. Hospital Universitario 12 de Octubre, Madrid, Spain Dpto. Bioquimica, Biologia Molecular y Celular, Universidad de Zaragoza Servicio de Inmunologia, Hospital Ramon y Cajal, Madrid, Spain * Corresponding author; email: lallende.hdoc{at}salud.madrid.org. Autoimmune lymphoproliferative syndrome (ALPS) is a disorder characterized by lymphoproliferation and autoimmune clinical manifestations and is generally caused by a defective Fas-mediated apoptosis. This report describes the first homozygous FasL gene mutation in a woman with clinical and immunological 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 bearing the high-producer genotype - 844C/C in her 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 eight different species from human support the essential role of FasL COOH terminal domain in Fas/FasL binding. These findings provide evidence that inherited nonlethal FasL abnormalities causes an uncommon apoptosis defect producing lymphoproliferative disease and 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]

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