IFN-γ and IgG responses to Mycobacterium tuberculosis latency antigen Rv2626c differentiate remote from recent tuberculosis infection

Abstract

Tuberculin skin test (TST) and IFN-γ release assays are currently used to detect Mycobacteriumtuberculosis (Mtb) infection but none of them differentiate active from latent infection (LTBI). Sinceimproved tests to diagnose Mtb infection are required, we studied the immune response to Mtb latencyantigen 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, TSTand IFN-γ secretion to Rv2626c were analyzed. Twenty-two percent of the individuals assessed haddiscordant results between QFT and TST tests. Furthermore, QFT negative and QFT positive individualsproduced differential levels of IFN-γ against Rv2626c, in direct association with their exposure periodto Mtb. Actually, 91% of CC QFT negative subjects secreted low levels of IFN-γ to Rv2626c, whereas43% of HW QFT negative people produced elevated IFN-γ amounts against Rv2626c. Conversely, 69%of CC QFT positive subjects didn´t produce IFN-γ to Rv2626c. Interestingly, a similar pattern of IgGanti-Rv2626c plasma levels was observed. Therefore, determination of IFN-γ and IgG levels against thedormancy antigen Rv2626c allows to identify established LTBI.