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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Abstract

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, Аustralia) carried out. Values of spontaneous (NIL) and antigen-induced (AG) production of10 cytokines (EGF, MIP-1p, VEGF, IL-2, IL-4, IL-6, IL-1a, IFN-a2, TGFa, TNFa) as well as sIL-2Ra and sCD40L using XMap technology were measured. IP-10 level was also determined in 48 individuals by using EIA. Results. 6 out of13 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 IFNy Ao -NIL, TGFa NIL and IL-6 AG 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 IFNyag -nil (r=0.71 and 0.79, respectively). Conclusion. IL-2 and IP-10 as well as IFNy may be used as helpful biomarkers as a first stage for diagnostics of (M.tb.) infection. At the second stage determination of IL-6, IFNy and TGFa for differential diagnostics of active TB and LTBI is proposed.

About the authors

E. V Vasilieva

Pasteur Research Institute of Epidemiology and Microbiology, Russia

V. N Verbov

Pasteur Research Institute of Epidemiology and Microbiology, Russia

V. B Ivanovsky

City Tuberculosis Dispensary, St. Petersburg, Russia

M. F Zhemkova

City Tuberculosis Dispensary, St. Petersburg, Russia

I. Yu Nikitina

Central Research Institute of Tuberculosis, Moscow, Russia

I. V Lyadova

Central Research Institute of Tuberculosis, Moscow, Russia

A. Totolyan Areg

Pasteur Research Institute of Epidemiology and Microbiology, Russia

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Copyright (c) 2013 Vasilieva E.V., Verbov V.N., Ivanovsky V.B., Zhemkova M.F., Nikitina I.Y., Lyadova I.V., Areg A.T.

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