TY - SER AU - Ruiz García, Raquel AU - Mora Diaz, Sergio AU - Paz Artal, Estela AU - Ruiz Contreras, Jesús AU - González Granados, Luis Ignacio AU - Allende Martínez, Luis Miguel ED - Servicio de Pediatría-Neonatología ED - Servicio de Inmunología ED - Instituto de Investigación imas12 TI - Decreased activation-induced cell death by EBV-transformed B-cells from a patient with autoimmune lymphoproliferative syndrome caused by a novel FASLG mutation. PY - 2015/// PB - Pediatric research N1 - Formato Vancouver: Ruiz García R, Mora S, Lozano Sánchez G, Martínez Lostao L, Paz Artal E, Ruiz Contreras J et al. Decreased activation-induced cell death by EBV-transformed B-cells from a patient with autoimmune lymphoproliferative syndrome caused by a novel FASLG mutation. Pediatr Res. 2015 Dec;78(6):603-8.; PMID: 26334989; Contiene 19 referencias N2 - Background: Autoimmune lymphoproliferative syndrome (ALPS) is a primary immunodeficiency characterized by chronic lymphoproliferation, autoimmune manifestations, expansion of double-negative T-cells, and susceptibility to malignancies. Most cases of ALPS are caused by germline or somatic FAS mutations. We report the case of an ALPS patient due to a novel homozygous Fasligand gene mutation (ALPS-FASLG). Methods: ALPS biomarkers were measured and FASLG mutation was identified. Functional characterization was carried out based on activation-induced cell death (AICD) and cytotoxicity assays. Results: This report describes the cases of a patient who presented a severe form of ALPS-FASLG, and his brother who had died due to complications related to ALPS. Moreover, in another family, we present the first case of lymphoma in a patient with ALPS-FASLG. Functional studies showed defective Fasligand-mediated apoptosis, cytotoxicity, and AICD in T-cell blasts. Otherwise, expression of the FASLG gene and corresponding protein was normal, but the shedding of the Fasligand was impaired in T-cells. Additionally, analyzing Epstein-Barr virus (EBV)-transformed B-cells, our results indicate impaired AICD in ALPS-FASLG patients. Conclusion: Patients with autosomal recessive inheritance of ALPS-FASLG have a severe phenotype and a partial defect in AICD in T- and B-cell lines. The Fasligand could play a key role in immune surveillance preventing malignancy UR - http://pc-h12o-es.m-hdoct.a17.csinet.es/pdf/pc/1/pc16912.pdf ER -