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Free Content Functional and genetic assessment of IFN-γ receptor in patients with clinical tuberculosis

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Abstract:

OBJECTIVE: The molecular basis of the genetic vulnerability underlying the most common form of clinical tuberculosis (TB) remains largely unknown. We speculated that mild genetic defects in the interferon-gamma (IFN-γ) signalling pathway caused a subtle functional impairment of IFN-γ which would explain susceptibility to Mycobacterium tuberculosis in clinical TB.

DESIGN: A case-control study.

RESULTS: We evaluated functional responsiveness to IFN-γ in monocytes from patients with clinical TB (n = 10), and analysed the genetic sequences of the IFN-γ receptor 1 (IFN-γR1) and STAT1 genes in patients with disseminated TB (n = 18). IFN-γ stimulated an increase in the expression of HLA-DR and CD64 on monocytes of both controls and patients; the rate of increase in expression was the same in both groups. Treatment with IFN-γ before lipopolysaccharide (LPS) stimulation further increased tumour necrosis factor-alpha (TNF-α) production as compared to TNF-α production with LPS stimulation alone; the rate of increase in TNF-α production was the same in both groups. The known mutations in the coding sequences of the IFN-γR1 and STAT1 genes were not found in the patients with disseminated tuberculosis.

CONCLUSION: These results suggest that impairment of the IFN-γ signalling pathway did not account for cases of clinical TB in this study.

Keywords: CD64; HLA-DR; IFN-γ; IFN-γ receptor; TNF-α; tuberculosis

Document Type: Regular Paper

Affiliations: 1: Department of Internal Medicine, Gachon Medical School, Gil Medical Centre, Incheon, South Korea 2: Department of Clinical Pathology, Gachon Medical School, Gil Medical Centre, Incheon, South Korea 3: Divison of Biological Science, Department of Molecular Biology, Gachon Medical School, Gil Medical Centre, Incheon, South Korea

Publication date: 2004-10-01

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  • The International Journal of Tuberculosis and Lung Disease publishes articles on all aspects of lung health, including public health-related issues such as training programmes, cost-benefit analysis, legislation, epidemiology, intervention studies and health systems research. The IJTLD is dedicated to the continuing education of physicians and health personnel and the dissemination of information on tuberculosis and lung health world-wide.

    Certain IJTLD articles are selected for translation into French, Spanish, Chinese or Russian. They are available on the Union website

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