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

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.

The priming effect of IFN-gamma and numbers of IFN-gamma receptors in patients with chronic refractory tuberculosis / 결핵

BACKGROUND: IFN-gamma plays an important role in host response to intracellular organisms such as mycobacterium. Human infection with mycobacterium leads to a wide variety of outcomes, ranging from asymptomatic infection to widespread and rapidly fatal disease. Recent reports suggest that alteration of the function of IFN-gamma caused by a defective IFN-gamma receptor gene can explain different host response to mycobacterium. In this study, we investigated the role of IFN-gamma in the development of chronic refractory tuberculosis. METHODS: The LPS-induced TNF-alpha production with or without IFN-gamma priming was compared by using monocytes taken from recently diagnosed tuberculosis, chronic refractory tuberculosis patients and controls. And the IFN-gamma receptor was measured by indirect fluorescent antibody technique to know whether change in the priming effect of IFN-gamma is related to IFN-gamma receptor deficiency or not. RESULTS: The ratio of TNF-alpha produced in response to stimulation with INF-gamma and LPS to LPS alone was 13.5 +/- 7.6 in controls, 10.8 +/- 6.4 in recently diagnosed tuberculosis patients and 6.7 +/- 3.9 in chronic refractory tuberculosis patients. The priming effect of IFN-gamma significantly decreased in chronic refractory tuberculosis patients compared with that in controls (p=0.002). However, IFN-gamma receptor deficiency was detected in one of chronic refractory tuberculosis patients. CONCLUSION: The decrease of the priming effect of IFN-gamma may play an important role in the development of chronic refractory tuberculosis, and in some patients, this may be related to the IFN-gamma receptor deficiency.