A Mycobacterium tuberculosis dormancy antigen differentiates latently infected Bacillus Calmette-Guérin -vaccinated individuals

PEÑA, D; ROVETTA, A; HERNANDEZ DEL PINO, R; AMIANO, N; PASQUINELLI, V; PELLEGRINI, J; TATEOSIAN, NANCY; ROLANDELLI, A; GUTIERREZ, M; MUSELLA, R; PALMERO, D; GHERARDI, MM; IOVANNA, J; CHULUYAN, E; GARCIA, V

EBioMedicine

ELSEVIER

Año: 2015 vol. 2 p. 882 - 888

2352-3964

IFN-γ release assays (IGRAs) are better indicators of Mycobacterium tuberculosis infection than the tuberculin skintest (TST) in Bacillus Calmette?Guérin (BCG)-vaccinated populations. However, IGRAs do not discriminate activeand latent infections (LTBI) and no gold standard for LTBI diagnosis is available. Thus, since improved tests to diagnoseM. tuberculosis infection are required, we assessed the efficacy of several M. tuberculosis latency antigens.BCG-vaccinated healthy donors (HD) and tuberculosis (TB) patients were recruited. QuantiFERON-TB GoldIn-Tube, TST and clinical data were used to differentiate LTBI. IFN-γ production against CFP-10, ESAT-6,Rv2624c, Rv2626c and Rv2628 antigens was tested in peripheral blood mononuclear cells. LTBI subjects secretedsignificantly higher IFN-γ levels against Rv2626c than HD. Additionally, Rv2626c peptide pools to which onlyLTBI responded were identified, and their cumulative IFN-γ response improved LTBI discrimination. Interestingly,whole blood stimulation with Rv2626c allowed the discrimination between active and latent infections, sinceTB patients did not secrete IFN-γ against Rv2626c, in contrast to CFP-10 + ESAT-6 stimulation that induced IFN-γresponse from both LTBI and TB patients. ROC analysis confirmed that Rv2626c discriminated LTBI from HD andTB patients. Therefore, since only LTBI recognizes specific epitopes from Rv2626c, this antigen could improve LTBIdiagnosis, even in BCG-vaccinated people.