Cytokine secretion and NK cell activity in human ADAM17 deficiency.
Oncotarget
; 6(42): 44151-60, 2015 Dec 29.
Article
en En
| MEDLINE
| ID: mdl-26683521
ABSTRACT
Genetic deficiencies provide insights into gene function in humans. Here we describe a patient with a very rare genetic deficiency of ADAM17. We show that the patient's PBMCs had impaired cytokine secretion in response to LPS stimulation, correlating with the clinical picture of severe bacteremia from which the patient suffered. ADAM17 was shown to cleave CD16, a major NK killer receptor. Functional analysis of patient's NK cells demonstrated that his NK cells express normal levels of activating receptors and maintain high surface levels of CD16 following mAb stimulation. Activation of individual NK cell receptors showed that the patient's NK cells are more potent when activated directly by CD16, albeit no difference was observed in Antibody Depedent Cytotoxicity (ADCC) assays. Our data suggest that ADAM17 inhibitors currently considered for clinical use to boost CD16 activity should be cautiously applied, as they might have severe side effects resulting from impaired cytokine secretion.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Leucocitos Mononucleares
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Células Asesinas Naturales
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Activación de Linfocitos
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Citocinas
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Proteínas ADAM
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Síndromes de Inmunodeficiencia
Tipo de estudio:
Diagnostic_studies
Límite:
Child, preschool
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Humans
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Male
Idioma:
En
Revista:
Oncotarget
Año:
2015
Tipo del documento:
Article
País de afiliación:
Israel