Zhurnal mikrobiologii, epidemiologii i immunobiologii · 2013
[Combined determination of spontaneous and antigen-induced production of cytokines for differential diagnostics of active tuberculosis of lungs and latent tuberculosis infection].
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Vasil'eva E V, Verbov V N, Ivanovskiĭ V B, Zhemkova M F, Nikitina I Iu, Liadova I V, Tatolian A A
Аннотация
AIM: Choice of informative biomarkers for diagnostics of Mycobacterium tuberculosis infection and differential diagnostics of active tuberculosis (TB) of lungs and latent tuberculosis infection (LTBI).
MATERIALS AND 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).
CONCLUSION: 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.
MATERIALS AND 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).
CONCLUSION: 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.