Novel nonsense IL-12R β1 mutation associated with recurrent tuberculosis

AbstractThe 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 theIL-12R β1 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 pat ient’s peripheral blood mononuclear cells (PBMCs) revealed significantly reduced IFNγ production. Flow cytometric analysis revealed no surface expression of IL-12Rβ1 on PHA-activated T lymphocytes. In addition, IL-12-induced impaired STAT4 phosphorylation in the patient’s lymphocytes when comp ared with those from five healthy controls. The genetic analysis ofIL-12R β1 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-12R β1 deficiency. Moreover, our findings highlight the need for developing newbo...
Source: Immunologic Research - Category: Allergy & Immunology Source Type: research