Ifn-Gamma And Igg Responses To Mycobacterium Tuberculosis Latency Antigen Rv2626c Differentiate Remote From Recent Tuberculosis Infection

Tuberculin skin test (TST) and IFN-gamma release assays are currently used to detect Mycobacterium tuberculosis (Mtb) infection but none of them differentiate active from latent infection (LTBI). Since improved tests to diagnose Mtb infection are required, we studied the immune response to Mtb latency antigen Rv2626c in individuals exposed to the bacteria during different periods. Tuberculosis patients (TB), TB close contacts (CC: subjects exposed to Mtb for less than three months) and healthcare workers (HW: individuals exposed to Mtb at least two years) were recruited and QuantiFERON (QFT) assay, TST and IFN-gamma secretion to Rv2626c were analyzed. Twenty-two percent of the individuals assessed had discordant results between QFT and TST tests. Furthermore, QFT negative and QFT positive individuals produced differential levels of IFN-gamma against Rv2626c, in direct association with their exposure period to Mtb. Actually, 91% of CC QFT negative subjects secreted low levels of IFN-gamma to Rv2626c, whereas 43% of HW QFT negative people produced elevated IFN-gamma amounts against Rv2626c. Conversely, 69% of CC QFT positive subjects didn ' t produce IFN-gamma to Rv2626c. Interestingly, a similar pattern of IgG anti-Rv2626c plasma levels was observed. Therefore, determination of IFN-gamma and IgG levels against the dormancy antigen Rv2626c allows to identify established LTBI.