title: Ethnicity-tailored novel set of ESAT-6 peptides for differentiating active and latent tuberculosis.
abstract: Differentiation between active and latent TB is a diagnostic challenge in TB-endemic regions. The commercially available IFN-γ-release assays are unsuitable for achieving this discrimination. We, therefore, screened ESAT-6 and CFP-10 proteins through population coverage analysis to identify minimal sets of peptides that can discriminate between these two forms of TB in a North Indian population. Comparing the diagnostic performance of a set of 2 ESAT-6 peptides (positions: 16-36; 59-79) to that of the QuantiFERON(®)-TB Gold IT (QFTGIT) assay, we observed significant difference in IFN-γ and TNF-α levels between patients (n = 15) and their age- and sex-matched healthy household contacts (n = 15). While the mean (±SD) IFNγ titer was 241.8 (±219.24) IU/ml for patients, the same in controls was 564.2 (±334.82) IU/ml (p = 0.039). Similarly the TNFα response was significantly higher in patients, compared to controls (796.47 ± 175.21 IU/ml vs. 481.81 ± 378.72 IU/ml; p = 0.047). IL-4 response to these peptides was non- discriminatory between the two groups. The QFTGIT Assay, however, elicited no significant difference in IFN-γ, TNF-α or IL-4 levels. Hence we conclude that IFN-γ or TNF-α response to these ESAT-6 peptides has the potential to differentiate between active and latent TB in our population.
authors.affiliation: Department of Microbiology, Himalayan Institute of Medical Sciences, Swami Ram Nagar, Jolly Grant, Dehradun 248140, Uttarakhand, India.
authors.forename: Salam Bhopen
authors.initials: SB
authors.lastname: Singh
authors.forename: Debasis
authors.initials: D
authors.lastname: Biswas
authors.forename: Jagdish
authors.initials: J
authors.lastname: Rawat
authors.forename: Girish
authors.initials: G
authors.lastname: Sindhwani
authors.forename: Abhishek
authors.initials: A
authors.lastname: Patras
authors.forename: Suraj
authors.initials: S
authors.lastname: Devrani
authors.forename: Pronoti
authors.initials: P
authors.lastname: Sarkar
authors.forename: Soumik
authors.initials: S
authors.lastname: Mitra
authors.forename: Shailendra K
authors.initials: SK
authors.lastname: Gupta
mesh_terms: D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007194:India / Q000453:epidemiology; D007371:Interferon-gamma / Q000096:biosynthesis; D059425:Interferon-gamma Release Tests / Q000379:methods; D015847:Interleukin-4 / Q000096:biosynthesis; D055985:Latent Tuberculosis / Q000175:diagnosis* / Q000208:ethnology; D008297:Male; D009169:Mycobacterium tuberculosis / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D010865:Pilot Projects; D011933:Reagent Kits, Diagnostic; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis* / Q000208:ethnology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C117940:CFP-10 protein, Mycobacterium tuberculosis; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D010446:Peptide Fragments; D011933:Reagent Kits, Diagnostic; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007371:Interferon-gamma
keywords: ATB; Active tuberculosis; CFP-10; ESAT-6; HHC; IEDB; IU; Immunodiagnosis; Latent tuberculosis; Mtb; Mycobacterium tuberculosis; OPD; PHA; PPD; Peptides; QFTGIT; QuantiFERON TB gold in tube; SD; SPSS; TST; active tuberculosis; culture filtrate protein 10; early secretory antigenic target 6; healthy household contact; immune epitope database; international unit; outdoor patients department; phytohaemagglutinin; purified protein derivative; standard deviation; statistical package for the social sciences; tuberculin skin test