Abstract
Tuberculin skin test (TST) and IFN-γ 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-γ 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-γ against Rv2626c, in direct association with their exposure period to Mtb. Actually, 91% of CC QFT negative subjects secreted low levels of IFN-γ to Rv2626c, whereas 43% 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 IgG anti-Rv2626c plasma levels was observed. Therefore, determination of IFN-γ and IgG levels against the dormancy antigen Rv2626c allows to identify established LTBI.
Highlights
Tuberculosis (TB) is the leading cause of decease by a single infectious agent and one of the top 10 causes of death worldwide
CC comprised subjects who had lived or worked with recently diagnosed pulmonary Tuberculosis patients (TB) patients for less than three months during 6 or more hours each day; healthcare workers (HW) included physicians and nurses who had worked at Hospital areas where TB patients were confined at least for two years; TB patients were subjects diagnosed with active disease (90% of them displayed acid-fast bacilli (AFB) smear-positive sputum)
These results suggest that the IFN-γ response induced against QuantiFERON-TB Gold Plus kit (QFT) antigens (ESAT-6 and CFP-10) fluctuates according to the exposure time of subject to Mycobacterium tuberculosis (Mtb), whereas the delayed hypersensitivity to tuberculin is independent of the exposure time of the individual to the pathogen
Summary
Tuberculosis (TB) is the leading cause of decease by a single infectious agent and one of the top 10 causes of death worldwide. Current IGRAs employ ESAT-6 and CFP-10, two antigens encoded in the region of difference 1 locus present in both Mtb and in M. bovis genomes[4]. Most environmental mycobacteria, which makes IGRAs more specific than TST4 Both assays only detect individuals who has been infected with Mtb, but they do not differentiate between latent and active Mtb infection[5,6]. Our results demonstrate that both IFN-γ and IgG responses against Rv2626c allow discriminating subjects with established latent Mtb infection from individuals recently exposed to the pathogen. These findings might represent an advantageous tool for the improvement of established LTBI diagnosis
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