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Volume 45, Number 6, December 2012

Impact of molecular diagnosis on treating Mendelian susceptibility to mycobacterial diseases

Li-Hui Wang, Chia-Liang Yen, Tsung-Chain Chang, Ching-Chuan Liu, Chi-Chang Shieh

Received: August 8, 2012    Revised: August 14, 2012    Accepted: August 20, 2012   


Corresponding author:
  • Department of Pediatrics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
  • Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan
  • Corresponding Author InformationCorresponding author. Institute of Clinical Medicine, National Cheng-Kung University, 138 Sheng-Li Road, Tainan 70403, Taiwan.


Background and purpose: 

The IL-12–IFN-γ axis is critical for immune defense against mycobacterial infections. Inherited mutations that affect normal activation of this self-amplifying cytokine reaction lead to increased chances of mycobacterial infections, known as Mendelian susceptibility to mycobacterial diseases (MSMD). Delayed diagnosis and difficulty in identifying pathogenic mycobacteria hinder proper treatment of patients, so the aim of this study was to facilitate the diagnosis of mycobacterial infections in MSMD patients using an oligonucleotide array method.



Peripheral blood mononuclear cells (PBMCs) were isolated from three MSMD patients in the same family. A series of immunologic studies, including testing for cytokine secretion after leukocyte stimulation, cell-surface marker analysis, and cDNA sequencing, were then performed. An oligonucleotide array was used to rapidly identify pathogens.



Cytokine secretion testing showed normal IFN-γ secretion after IL-12 stimulation but low IL-12 secretion after IFN-γ stimulation, which indicates a defect in the IFN-γ receptor or its intracellular signaling. Cell-surface receptor analysis showed IFN-γ receptor 1 overexpression, suggesting an autosomal dominant IFN-γ receptor 1 deficiency. cDNA sequencing identified the IFNGR1 818del4 mutation in three members of the family with known MSMD, and an oligonucleotide array identified Mycobacterium tuberculosis complex and Mycobacterium abscessus as pathogens.



Patients with suspected MSMD should undergo molecular diagnosis of the primary immunodeficiency. Oligonucleotide array methods may be a tool for rapid identification of pathogens and for guiding antimicrobial treatment in immunodeficient patients.


Key words:

Autosomal dominant interferon-γ receptor 1 deficiencyMycobacterial infectionOligonucleotide arrayPrimary immunodeficiency disease