IFN-γ/TNF-α ratio in response to immuno proteomically identified human T-cell antigens of Mycobacterium tuberculosis - The most suitable surrogate biomarker for latent TB infection

The enormous reservoir of latent TB infection (LTBI) poses a major hurdle for global TB control. The existing Tuberculin skin test (TST) and IFN-gamma release assays (IGRAs) are found to be suboptimal for LTBI diagnosis. Previously we had taken an immunoproteomic approach and identified 10 protein fractions (contains 16 proteins), which are solely recognized by LTBI. In a cohort of 40 pulmonary TB patients (PTB) and 35 healthy household contacts (HHC), IFN-gamma and TNF-alpha response were measured against 16 antigens by using 1: 10 diluted whole blood assay. Among all the antigens, IFN-gamma response to Rv2626c has shown positivity of 88.57% in HHC and 7.5% in PTB group. IFN-gamma response to combination of Rv2626c + Rv3716c has demonstrated 100% positivity in HHC and 17.5% positivity in PTB respectively. Compared to individual cytokines (i.e. IFN-gamma and TNF-alpha), ratio of IFN-gamma/TNF-alpha has shown promising results for diagnosis of LTBI. IFN-gamma/TNF-alpha ratio against Rv3716c and TrxC has exhibited a positivity of 94.29% in HHC and 5% in PTB group. Accession of Rv2626c and Rv3716c may improve the diagnostic performance of existing QFT-GIT. Independent of QFT-GIT assay, ratio of IFN-gamma/TNF-alpha in response to either Rv3716c or TrxC may acts as suitable surrogate biomarker for LTBI. (C) 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.