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-γ 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-γ and TNF-α response were measured against 16 antigens by using 1:10 diluted whole blood assay. Among all the antigens, IFN-γ response to Rv2626c has shown positivity of 88.57% in HHC and 7.5% in PTB group. IFN-γ 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-γ and TNF-α), ratio of IFN-γ/TNF-α has shown promising results for diagnosis of LTBI. IFN-γ/TNF-α 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-γ/TNF-α in response to either Rv3716c or TrxC may acts as suitable surrogate biomarker for LTBI.