The value of transcriptomics in advancing knowledge of the immune response and diagnosis in tuberculosis

Abstract

Blood transcriptomics in tuberculosis have revealed an IFN-inducible signature that diminished upon successful treatment, promising improved diagnostics and treatment monitoring, essential to eradicate tuberculosis. Sensitive radiography revealing lung abnormalities and blood transcriptomics have demonstrated heterogeneity in active tuberculosis patients and exposed asymptomatic latent individuals, suggesting a continuum of infection and immune states. Here, we describe the immune response to M. tuberculosis infection revealed using transcriptomics, and differences between clinical phenotypes of infection that may inform temporal changes in host immunity associated with evolving infection. We also review the diverse reduced blood transcriptional gene signatures that have been proposed for tuberculosis diagnosis and identification of at-risk asymptomatic individuals, and suggest novel approaches for developing such biomarkers for clinical use.

Concise whole blood transcriptional signatures for incipient tuberculosis: A systematic review and patient-level pooled meta-analysis

“…The most likely application of this technology is therefore likely to be diagnosis of incipient TB, where the WHO TPP pricing parameters are more lenient, aiming for an initial price of <$100, with the price of IGRAs as an initial benchmark 8 . The application of these biomarkers for incipient TB diagnosis also mitigates the major limitation of the imperfect specificity of predominantly interferon-inducible gene signatures when trying to discriminate TB from other infectious diseases, by applying them to a predominantly healthy and asymptomatic population 36 . The equivalence of diagnostic accuracy of eight signatures for incipient TB in this analysis suggests that parsimony of genes, stability of cross-platform transcript measurements, and simplicity of modelling calculations may be key to informing selection of signatures from these candidates for further validation.…”

Transcriptional Profiling of Human Peripheral Blood Mononuclear Cells Identifies Diagnostic Biomarkers That Distinguish Active and Latent Tuberculosis

“…However, TST and commercial IGRA tests cannot distinguish latent infection from active disease (24). Previously identified biomarkers of active and latent infection vary considerably among studies, limiting their utility for clinical diagnosis (25,26). This variation may be explained by the complexity of the infection and disease continuum as well as variation in immune responses during the infection process.…”

Blood RNA Signatures Predict Recent Tuberculosis Exposure in Mice, Macaques and Humans

“…Another potential benefit of such a study is that validated biomarkers that associate strongly with TST/IGRA conversion but precede conversion, such as currently M.tb infection that can be reproducibly measured (34). Future biomarker studies may enable the study of early events of infection in humans both routinely and ethically and permit the identification of immunological or other biological events that determine whether an exposed person will develop TB disease or control the infection (5,(53)(54)(55). This could greatly aid vaccine development for TB as no correlates of protection for TB are yet known (56).…”