Magnesium Restores Activity to Peripheral Blood Cells in a Patient With Functionally Impaired Interleukin-2-Inducible T Cell Kinase.
Front Immunol
; 10: 2000, 2019.
Article
en En
| MEDLINE
| ID: mdl-31507602
ABSTRACT
Interleukin-2-inducible T cell kinase (ITK) is critical for T cell signaling and cytotoxicity, and control of Epstein-Barr virus (EBV). We identified a patient with a novel homozygous missense mutation (D540N) in a highly conserved residue in the kinase domain of ITK who presented with EBV-positive lymphomatoid granulomatosis. She was treated with interferon and chemotherapy and her disease went into remission; however, she has persistent elevation of EBV DNA in the blood, low CD4 T cells, low NK cells, and nearly absent iNKT cells. Molecular modeling predicts that the mutation increases the flexibility of the ITK kinase domain impairing phosphorylation of the protein. Stimulation of her T cells resulted in reduced phosphorylation of ITK, PLCγ, and PKC. The CD8 T cells were moderately impaired for cytotoxicity and degranulation. Importantly, addition of magnesium to her CD8 T cells in vitro restored cytotoxicity and degranulation to levels similar to controls. Supplemental magnesium in patients with mutations in another protein important for T cell signaling, MAGT1, was reported to restore EBV-specific cytotoxicity. Our findings highlight the critical role of ITK for T cell activation and suggest the potential for supplemental magnesium to treat patients with ITK deficiency.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Células Sanguíneas
/
Proteínas Tirosina Quinasas
/
Susceptibilidad a Enfermedades
/
Magnesio
Tipo de estudio:
Diagnostic_studies
/
Etiology_studies
/
Prognostic_studies
Límite:
Adult
/
Female
/
Humans
Idioma:
En
Revista:
Front Immunol
Año:
2019
Tipo del documento:
Article
País de afiliación:
Estados Unidos