Granzyme A as a potential biomarker of Mycobacterium tuberculosis infection and disease

• In our study we have investigated the potential role of granzyme A levels in plasma obtained from stimulated whole blood, as biomarker of infection/disease comparing patients with active TB disease with LTBI subjects.
• The current challenge was to identify markers that are specific and unique for TB that could represent a specific signature when compared with other infectious diseases which have high clinical similarity to TB.
• In conclusion, our results suggest that granzyme A could be considered a new additional biomarker of TB, that can be used, other than IFN-γ, to identify subjects infected by Mtb with the limit due to not discriminate between active TB and LTBI.
• Further studies are thus required to confirm these data in a larger number of patients and to evaluate the possible implications in terms of TB risk.

Cytotoxic molecules such as granulysin, perforin and granzymes produced by cytolytic T cells directly contribute to immune defense against tuberculosis (TB). In search for novel TB biomarkers, we have evaluated the levels of granzyme A in plasma obtained from QuantiFERON-TB Gold In tube (QFT-IT) assays from patients with active TB disease and subjects with latent TB infection (LTBI).Granzyme A serum levels in TB patients were significantly lower than values found in LTBI subjects even after subtraction of the unstimulated levels from the antigen-stimulated responses. The receiver operator characteristics (ROC) curve analysis comparing TB patients and LTBI groups, showed that at a cut-off value of granzyme A of <3.425 pg/ml, the sensitivity and the specificity of the assay were 29.41% and 94.74%, respectively.Our results suggest that granzyme A could be considered another biomarker of TB, that can be used, other than IFN-γ, to discriminate between patients with active TB and LTBI subjects in a well characterized cohort of confirmed Mycobacterium tuberculosis-infected individuals.