Differential T cell responses against DosR-associated antigen Rv2028c in BCG-vaccinated populations with tuberculosis infection - 24/03/19

Highlights |
• | The levels of Rv2028c-specific IFN-γ responses in whole blood were significantly higher in latent TB-infected (LTBI) individuals compared with active TB (ATB) patients. |
• | Rv2028c-specific IFN-γ responses can aid discrimination between healthy LTBI individuals and ATB patients in Mtb-infected populations. |
• | The combination of Rv2028c and ESAT-6/CFP10 in IFN-γ ELISA assays enhanced the diagnostic efficacy of active TB. |
• | Effective anti-TB drug treatment selectively elevated Rv2028c-specific IFN-γ responses in ATB patients. |
Summary |
The IFN-γ release assays (IGRAs) based on region of difference 1 (RD1) antigens have improved diagnosis of Mycobacterium tuberculosis (Mtb) infection. However, IGRAs with these antigens could not distinguish latent tuberculosis infection (LTBI) from active tuberculosis (ATB). DosR regulon genes are thought to be important for Mtb dormancy, and their products have higher immunogenicity in LTBI than ATB individuals, suggesting protective immunity mediated by DosR regulon-encoded antigens and potential utility of them for differential diagnostics of Mtb-infected populations or development of therapeutic vaccines against tuberculosis (TB). Among them, Rv2028c is a dormancy-related antigen that has demonstrated potential use in TB control, but its immunological characteristics in the BCG-vaccinated Chinese population are unknown. In this study, a total of 148 individuals, including 98 patients with ATB, 20 cases with LTBI and 30 healthy controls, were tested for Rv2028c-specific T cell responses by using an IFN-γ ELISA assay. The results showed that the T-cell responses in LTBI individuals were almost always higher than those in ATB patients, regardless of the site of infection or the results of bacteriological examination in the patients. This allowed for good differentiation between these two groups of Mtb-infected individuals even in the BCG-vaccinated high TB-incidence setting that pertains in China. In addition, the diagnostic efficacy for ATB was enhanced by combining the results from Rv2028c and RD1 antigen-based IFN-γ ELISA assays. In conclusion, Rv2028c-specific T-cell responses might contribute to natural protection against dormant Mtb infection, and the determination of these responses can aid discrimination between healthy LTBI individuals and ATB patients in the Mtb-infected populations.
Le texte complet de cet article est disponible en PDF.Graphical abstract |
Keywords : Mycobacterium tuberculosis, IFN-γ release assay, Rv2028c, Protective immunity, Latency antigen, DosR regulon
Plan
Vol 78 - N° 4
P. 275-280 - avril 2019 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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