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
; 78(6): 603-8, 2015 Dec.
Article
en En
| MEDLINE
| ID: mdl-26334989
ABSTRACT
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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Linfocitos B
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Transformación Celular Viral
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Herpesvirus Humano 4
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Citotoxicidad Inmunológica
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Proteína Ligando Fas
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Síndrome Linfoproliferativo Autoinmune
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Linfoma
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Mutación
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Adult
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Child, preschool
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Female
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Humans
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Infant
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Male
Idioma:
En
Revista:
Pediatr Res
Año:
2015
Tipo del documento:
Article
País de afiliación:
España