Novel nonsense IL-12Rß1 mutation associated with recurrent tuberculosis.
Immunol Res
; 67(4-5): 408-415, 2019 10.
Article
em En
| MEDLINE
| ID: mdl-31741236
ABSTRACT
The interleukin (IL)-12/interferon(IFN)γ axis plays an important role in the control of mycobacterial diseases as demonstrated by the increased susceptibility to mycobacterial species in patients with an inborn error of the IL-12-dependent IFNγ immunity. Here, we report a novel mutation in the IL-12Rß1 gene in a female Pakistani patient who was born in a consanguineous marriage and developed severe bacille Calmette-Guérin (BCG) infection and recurrent tuberculosis. After reviewing the patient's clinical records, she was investigated for IL-12/IFNγ defects using enzyme-linked immunosorbent assay (ELISA), flow cytometry, and DNA genetic Sanger sequencing. Quantification of secretory cytokines from the patient's peripheral blood mononuclear cells (PBMCs) revealed significantly reduced IFNγ production. Flow cytometric analysis revealed no surface expression of IL-12Rß1 on PHA-activated T lymphocytes. In addition, IL-12-induced impaired STAT4 phosphorylation in the patient's lymphocytes when compared with those from five healthy controls. The genetic analysis of IL-12Rß1 gene identified a novel nonsense mutation c.199G>T/p.E67* within exon 3, which encodes part of the cytokine-binding region (CBR). In silico analysis indicates that this novel nonsense mutation generates a truncated protein with an apparent inactivating effect. Our data expand the genetic spectrum of IL-12Rß1 deficiency. Moreover, our findings highlight the need for developing newborn screening for patients with primary immunodeficiency associated with mycobacterial infections in areas where BCG vaccination is mandatory in order to improve the treatment of patients, and consequently their quality of life.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tuberculose
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Códon sem Sentido
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Receptores de Interleucina-12
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Child
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Female
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Humans
Idioma:
En
Revista:
Immunol Res
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Paquistão