Abstract

The aim of our work here was to evaluate the immunogenicity of 60 mycobacterial antigens, some of which have not been previously assessed, notably a novel series of in vivo-expressed Mycobacterium tuberculosis (IVE-TB) antigens. We enrolled 505 subjects and separated them in individuals with and without latent tuberculosis infection (LTBI) vs. patients with active tuberculosis (TB). Following an overnight and 7 days stimulation of whole blood with purified recombinant M. tuberculosis antigens, interferon-γ (IFN-γ) levels were determined by ELISA. Several antigens could statistically significantly differentiate the groups of individuals. We obtained promising antigens from all studied antigen groups [dormancy survival regulon (DosR regulon) encoded antigens; resuscitation-promoting factors (Rpf) antigens; IVE-TB antigens; reactivation associated antigens]. Rv1733, which is a probable conserved transmembrane protein encoded in DosR regulon, turned out to be very immunogenic and able to discriminate between the three defined TB status, thus considered a candidate biomarker. Rv2389 and Rv2435n, belonging to Rpf family and IVE-TB group of antigens, respectively, also stood out as LTBI biomarkers. Although more studies are needed to support our findings, the combined use of these antigens would be an interesting approach to TB immunodiagnosis candidates.

Highlights

  • Tuberculosis (TB) remains one of the most death-causing microorganism worldwide (World Health Organization, 2013)

  • In this study we evaluated whether latency antigens induced a response which varied according to the group of individuals

  • Chegou et al (2012) observed that the majority of response to M.tb infection is largely driven by ESAT6/CFP-10, not by the other antigens that they used as controls (TB7.7, Ag85A/B, and HSP65), where the recognition was poor

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Summary

Introduction

Tuberculosis (TB) remains one of the most death-causing microorganism worldwide (World Health Organization, 2013). The main antigens used in IGRAs, the 6-kDa M.tb earlysecreted antigenic target (ESAT)-6 protein, 10-kDa culture filtrate protein (CFP-10), coded in the region of difference (RD) 1, and TB7.7, coded in RD11, are present in M.tb but not in any Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccine strain nor in the majority of non-tuberculous mycobacteria (Andersen et al, 2000) Their specificity is better than in TST, IGRAs do not discriminate between active disease and LTBI (Latorre et al, 2009) and do not clearly distinguish between a recently acquired infection and remote LTBI (Esmail et al, 2012; Pollock et al, 2013). Their sensitivity barely exceed 80%, and the response level against the antigens used does not seem to indicate high risk of progression to active TB

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