The Functional and Genetic Defects of IFN-gamma Receptor in the Patients with Tuberculosis.
10.4046/trd.2002.52.5.497
- Author:
Gye Young PARK
1
;
You Jin HWANG
;
Young Hee LIM
;
Chang Hyeok AN
;
Jeong Woong PARK
;
Seong Hwan JEONG
Author Information
1. Department of Internal Medicine, Gachon Medical School, Cil Medical Center, Incheon, Korea. parkgy@ghil.com
- Publication Type:Original Article
- Keywords:
Tuberculosis;
Disseminated tuberculosis;
IFN-gamma;
IFN-gamma receptor;
STAT1
- MeSH:
Clinical Coding;
DNA;
HLA-DR Antigens;
Humans;
Mycobacterium bovis;
Tuberculosis*;
Tumor Necrosis Factor-alpha
- From:Tuberculosis and Respiratory Diseases
2002;52(5):497-505
- CountryRepublic of Korea
- Language:Korean
-
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.
