Assessment of CD27 expression as a tool for active and latent tuberculosis diagnosis

- Active TB associates with Mycobacterium tuberculosis-specific CD45RA− CD27− CD4+ IFNγ+ T-cells.
- Active TB associates with M. tuberculosis-specific CD27− CD4+ IFN-γ+ T-cells.
- Active TB associates with a high CD27 MFI RATIO on Mtb-specific CD4+ T-cells.
- Several cytometric methods support the use of CD27 as a biomarker for active TB.
- The above immune-approaches have been studied among the IGRA-responsive subjects.

SummaryThere are still no reliable tests to distinguish active tuberculosis (TB) from latent TB infection (LTBI). Assessment of CD27 modulation on CD4+ T-cells has been suggested as a tool to diagnose different TB stages.ObjectivesTo use several cytometric approaches to evaluate CD27 expression on Mycobacterium tuberculosis (Mtb)-specific CD4+ T-cells to differentiate TB stages.Methods55 HIV-uninfected subjects were enrolled: 13 active TB; 12 cured TB; 30 LTBI. Whole blood was stimulated with RD1-proteins or Cytomegalovirus-lysate (CMV). Interferon (IFN)-γ response was evaluated by cytometry. The proportion of CD27−/+ within the IFN-γ+ CD4+ T-cells or RATIO of the CD27-median fluorescence intensity (MFI) of CD4+ T-cells over the CD27 MFI of IFN-γ+ CD4+ T-cells was evaluated.ResultsThe greatest diagnostic accuracy in discriminating active TB vs. LTBI or cured TB was reached by evaluating the CD27+ CD45RA− cells within the IFN-γ+ CD4+ T-cell subset (76.92 sensitivity for both, and 90% and 91.67% specificity, respectively), although the use of the CD27 MFI RATIO allows for stricter data analysis, independent of the operator.Conclusionsthe study of CD27 expression using different approaches, whether it involves evaluation of CD45RA expression or not, is a robust biomarker for discriminating TB stages.