title: Functional and genetic assessment of IFN-gamma receptor in patients with clinical tuberculosis.
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-gamma) signalling pathway caused a subtle functional impairment of IFN-gamma which would explain susceptibility to Mycobacterium tuberculosis in clinical TB.
  
  
  METHODS
  A case-control study.
  
  
  RESULTS
  We evaluated functional responsiveness to IFN-gamma in monocytes from patients with clinical TB (n = 10), and analysed the genetic sequences of the IFN-gamma receptor 1 (IFN-gammaR1) and STAT1 genes in patients with disseminated TB (n = 18). IFN-gamma 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-gamma before lipopolysaccharide (LPS) stimulation further increased tumour necrosis factor-alpha (TNF-alpha) production as compared to TNF-alpha production with LPS stimulation alone; the rate of increase in TNF-alpha production was the same in both groups. The known mutations in the coding sequences of the IFN-gammaR1 and STAT1 genes were not found in the patients with disseminated tuberculosis.
  
  
  CONCLUSIONS
  These results suggest that impairment of the IFN-gamma signalling pathway did not account for cases of clinical TB in this study.
authors.affiliation: Department of Internal Medicine, Gachon Medical School, Gil Medical Centre, Incheon, South Korea. parkgy@gachon.md
authors.forename: G Y
authors.initials: GY
authors.lastname: Park
authors.forename: Y H
authors.initials: YH
authors.lastname: Im
authors.forename: C H
authors.initials: CH
authors.lastname: Ahn
authors.forename: J W
authors.initials: JW
authors.lastname: Park
authors.forename: S W
authors.initials: SW
authors.lastname: Jeong
authors.forename: J Y
authors.initials: JY
authors.lastname: Ahn
authors.forename: Y J
authors.initials: YJ
authors.lastname: Hwang
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000235:genetics; D004198:Disease Susceptibility; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000276:immunology; D017452:Receptors, IgG / Q000032:analysis; D017471:Receptors, Interferon / Q000235:genetics*; D050794:STAT1 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics; D014376:Tuberculosis / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D000096743:Interferon gamma Receptor
chemical_list: D004268:DNA-Binding Proteins; D006684:HLA-DR Antigens; D008070:Lipopolysaccharides; D017452:Receptors, IgG; D017471:Receptors, Interferon; D050794:STAT1 Transcription Factor; D015534:Trans-Activators; D014409:Tumor Necrosis Factor-alpha; D000096743:Interferon gamma Receptor; C494079:STAT1 protein, human