title: [Combined determination of spontaneous and antigen-induced production of cytokines for differential diagnostics of active tuberculosis of lungs and latent tuberculosis infection].
abstract: OBJECTIVE
  Choice of informative biomarkers for diagnostics of Mycobacterium tuberculosis infection and differential diagnostics of active tuberculosis (TB) of lungs and latent tuberculosis infection (LTBI).
  
  
  METHODS
  54 tuberculosis patients, 47 contact by TB, individuals and 43 healthy donors were examined. All the individuals included into the study had QuantiFERON-TB Gold In-Tube (Cellestis, Australia) carried out. Values of spontaneous (NIL) and antigen-induced (AG) production of 10 cytokines (EGF, MIP-1beta, VEGF, IL-2, IL-4, IL-6, IL-1alpha, IFN-alpha2, TGFalpha, TNFalpha) as well as sIL-2Ralpha and sCD40L using XMap technology were measured. IP-10 level was also determined in 48 individuals by using EIA.
  
  
  RESULTS
  6 out of 13 biomarkers distinguished active TB and LTBI. As a result of construction of a decision tree in JMP 9.0 program 3 most significant markers were selected. Use of combination of IFN(gammaAG-NIL), TGFalpha NIL and IL-6AG cytokines allowed to divide TB patients and contact individuals with sensitivity of 96.3% and specificity of 80.7% (AUC = 0.9). We also observed very high levels of IP-10 and IL-2 that correlated with IFN(gammaAG-NIL) (r = 0.71 and 0.79, respectively).
  
  
  CONCLUSIONS
  IL-2 and IP-10 as well as IFNgamma may be used as helpful biomarkers as a first stage for diagnostics of (M.tb.) infection. At the second stage determination of IL-6, IFNgamma and TGFalpha for differential diagnostics of active TB and LTBI is proposed.
authors: E V
authors: EV
authors: Vasil'eva
authors: V N
authors: VN
authors: Verbov
authors: V B
authors: VB
authors: Ivanovskiĭ
authors: M F
authors: MF
authors: Zhemkova
authors: I Iu
authors: IIu
authors: Nikitina
authors: I V
authors: IV
authors: Liadova
authors: A A
authors: AA
authors: Tatolian
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000942:Antigens, Bacterial / Q000276:immunology; D015415:Biomarkers / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D055985:Latent Tuberculosis / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000378:metabolism / Q000472:pathogenicity; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D000942:Antigens, Bacterial; D015415:Biomarkers; D016207:Cytokines; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma