A Mycobacterium tuberculosis Dormancy Antigen Differentiates Latently Infected Bacillus Calmette?Guérin-vaccinated Individuals

DELFINA PEÑA; ANA I. ROVETTA; HERNÁNDEZ DEL PINO, RODRIGO E; AMIANO NICOLAS; PASQUINELLI VIRGINIA; JOAQUIN PELLEGRINI; NANCY TATEOSIAN; ROLANDELLI AGUSTIN; GUTIERREZ MARISA; ROSA M MUSELLA; DOMINGO PALMERO; MARIA MAGDALENA GHERARDI; JUAN IOVANNA; CHULUYAN, H. EDUARDO; VERONICA E GARCIA

EBioMedicine

Elsevier

Año: 2015

2352-3964

IFN-γ release assays (IGRAs) are better indicators of Mycobacterium tuberculosis infection than the tuberculin skin test (TST) in Bacillus Calmette-Guérin (BCG)-vaccinated populations. However, IGRAs do not discriminate active and latent infection (LTBI) and no gold standard for LTBI diagnosis is available. Thus, since improved tests to diagnose M. 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 Gold In-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 secreted significantly higher IFN-γ levels against Rv2626c than HD. Additionally, Rv2626c peptide pools to which only LTBI 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 infection, since TB patients did not secrete IFN-γ against Rv2626c, in contrast to CFP-10+ESAT-6 stimulation that induced IFN-γ response from both LTBI and TB patients. ROC analysis confirmed that Rv2626c discriminated LTBI from HD and TB patients. Therefore, since only LTBI recognize specific epitopes from Rv2626c, this antigen could improve LTBI diagnosis, even in BCG-vaccinated people.