Tuberc Respir Dis.  2002 May;52(5):497-505.

The Functional and Genetic Defects of IFN-gamma Receptor in the Patients with Tuberculosis

Affiliations
  • 1Department of Internal Medicine, Gachon Medical School, Cil Medical Center, Incheon, Korea. parkgy@ghil.com
  • 2Laboratory of Molecular Biology, Gachon Medical School, Cil Medical Center, Incheon, Korea.

Abstract

BACKGROUND: IFN-gamma plays an important role in the host response to a mycobacterial infection. A complete IFN-gamma receptor 1 deficiency is a life-threatening condition because it renders patients highly susceptible t o a mycobacterial infection. Several mutations in the IFN-gamma receptor and STAT1 gene have been identified in the rare mycobacterial infections. These mutations have partial function of the IFN-gamma receptor and similar pathologic features to clinical tuberculosis.
METHODS
The function of the IFN-gamma receptor was evluated in the patients with clinical tuerculosis. In addition, the DNA coding sequence of the IFNgR1 and STAT1 gene was also analyzed in disseminated tuberculosis patients who might have a defective IFN-gamma receptor.
RESULTS
The cell surface expression levels of HLA-DR and CD64 in the PMBC after being stimulation with IFN-gamma (100Imicro/ml, 1000Imicro/ml) were increased in both controls and patients. However, the rate of increase in both groups was similar. The production of TNF-alpha in the response to stimulation with LPS was higher in the both groups (850.7+/-687.8 vs. 836.7+/-564.3 pg/ml). Pretreatment with IFN-gamma prior to LPS stimulation resulted infurther increase in TNF-alpha production in the both groups was similar. The known mutations in the IFNgR1 and STAT1 coding sequences were not found in the genomic DNA of patients wit disseminated tuberculosis.
CONCLUSION
The functional and genetic defects of the IFN-gamma receptor were not identified in clinical tuberculosis. This suggests the defective IFN-gamma receptor that predispoe patiens to a BCG or NTM infection can not alone account for the cases of clinical tuberculosis.

Keyword

Tuberculosis; Disseminated tuberculosis; IFN-gamma; IFN-gamma receptor; STAT1

MeSH Terms

Clinical Coding
DNA
HLA-DR Antigens
Humans
Mycobacterium bovis
Tuberculosis*
Tumor Necrosis Factor-alpha
DNA
HLA-DR Antigens
Tumor Necrosis Factor-alpha
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