Are mRNA based transcriptomic signatures ready for diagnosing tuberculosis in the clinic? - A review of evidence and the technological landscape

Hamada, Yohhei; Penn-Nicholson, Adam; Krishnan, Sriram; Cirillo, Daniela María; Matteelli, Alberto; Wyss, Romain; Denkinger, Claudia M.; Rangaka, Molebogeng X; Rühwald, Morten; Schumacher, Samuel G

doi:10.1016/j.ebiom.2022.104174

Cited by 21 publications

(20 citation statements)

References 61 publications

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“…Finally, efforts to develop a point-of-care testing platform with more refined transcriptomic signatures have already been done, although studies have mostly been conducted in terms of a triage or a diagnostic test for active TB, rather than an incipient TB test [ 29 , 42 ]. A recent study using the Cepheid MTB Host Response cartridge with fingerpricked blood samples, applying the Sweeney3-gene signature, showed promising performance as a point-of-care triage test for active TB [ 29 ].…”

Section: Host Transcriptional Signatures For Predicting Progression T...mentioning

confidence: 99%

“…Most studies were performed in specific regions, such as Africa and the UK. The performance of the signature derived from a cohort was different when applied to other cohorts, suggesting heterogeneity in gene expression across different populations [ 24 , 42 ]. Thus, these performances need to be validated by testing the generalized population with variable genetic backgrounds, diverse strains of MTB, and different environmental exposures [ 18 , 42 ].…”

Section: Host Transcriptional Signatures For Predicting Progression T...mentioning

confidence: 99%

“…The performance of the signature derived from a cohort was different when applied to other cohorts, suggesting heterogeneity in gene expression across different populations [ 24 , 42 ]. Thus, these performances need to be validated by testing the generalized population with variable genetic backgrounds, diverse strains of MTB, and different environmental exposures [ 18 , 42 ]. Furthermore, transcriptional signatures can also be affected by individual characteristics such as age, immunosuppressive condition, and other comorbidities.…”

Section: Host Transcriptional Signatures For Predicting Progression T...mentioning

confidence: 99%

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Host Blood Transcriptional Signatures as Candidate Biomarkers for Predicting Progression to Active Tuberculosis

Kim¹,

Choi²,

Lee³

2023

Tuberc Respir Dis

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A recent understanding of the dynamic continuous spectrum of <i>Mycobacterium tuberculosis</i> infection has led to the recognition of incipient tuberculosis, which refers to the latent infection state that has begun to progress to active tuberculosis. The importance of early detection of these individuals with a high-risk of progression to active tuberculosis is emphasized to efficiently implement targeted tuberculosis preventive therapy. However, the tuberculin skin test or interferon-γ release assay, which is currently used for the diagnosis of latent tuberculosis infection, does not aid in the prediction of the risk of progression to active tuberculosis. Thus, a novel test is urgently needed. Recently, simultaneous and systematic analysis of differentially expressed genes using a high-throughput platform has enabled the discovery of key genes that may serve potential biomarkers for the diagnosis or prognosis of diseases. This host transcriptional investigation has been extended to the field of tuberculosis, providing promising results. The present review focuses on recent progress and challenges in the field of blood transcriptional signatures to predict progression to active tuberculosis.

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Section: Host Transcriptional Signatures For Predicting Progression T...mentioning

confidence: 99%

Section: Host Transcriptional Signatures For Predicting Progression T...mentioning

confidence: 99%

Section: Host Transcriptional Signatures For Predicting Progression T...mentioning

confidence: 99%

See 1 more Smart Citation

Host Blood Transcriptional Signatures as Candidate Biomarkers for Predicting Progression to Active Tuberculosis

Kim¹,

Choi²,

Lee³

2023

Tuberc Respir Dis

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“…miRNAs are host short non-coding RNAs that interact with complementary mRNAs, resulting in positive regulation (transcription stimulation) or negative regulation (transcription inhibition or mRNA degradation) [ 173 ]. As shown in Table 4 , multiple miRNAs could also serve as biomarkers for ATB and TBI [ 174 , 175 , 176 , 177 , 178 ], but are probably not yet ready for everyday use in TB clinics [ 179 ]. In addition to miRNAs, one study showed that small nuclear RNA (snoRNA) and PIWI-interacting RNA (piRNA) are important biomarkers for TBI with potential participation in the TB pathophysiology [ 180 ].…”

Section: Evaluation Of Host-derived Biomarkersmentioning

confidence: 99%

Challenges and the Way forward in Diagnosis and Treatment of Tuberculosis Infection

et al. 2023

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Globally, it is estimated that one-quarter of the world’s population is latently infected with Mycobacterium tuberculosis (Mtb), also known as latent tuberculosis infection (LTBI). Recently, this condition has been referred to as tuberculosis infection (TBI), considering the dynamic spectrum of the infection, as 5–10% of the latently infected population will develop active TB (ATB). The chances of TBI development increase due to close contact with index TB patients. The emergence of multidrug-resistant TB (MDR-TB) and the risk of development of latent MDR-TB has further complicated the situation. Detection of TBI is challenging as the infected individual does not present symptoms. Currently, there is no gold standard for TBI diagnosis, and the only screening tests are tuberculin skin test (TST) and interferon gamma release assays (IGRAs). However, these tests have several limitations, including the inability to differentiate between ATB and TBI, false-positive results in BCG-vaccinated individuals (only for TST), false-negative results in children, elderly, and immunocompromised patients, and the inability to predict the progression to ATB, among others. Thus, new host markers and Mtb-specific antigens are being tested to develop new diagnostic methods. Besides screening, TBI therapy is a key intervention for TB control. However, the long-course treatment and associated side effects result in non-adherence to the treatment. Additionally, the latent MDR strains are not susceptible to the current TBI treatments, which add an additional challenge. This review discusses the current situation of TBI, as well as the challenges and efforts involved in its control.

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“…Moreover, in this study there was no assessment of blood transcriptional responses to vaccination, which we and others have shown to be important for identifying biomarkers of vaccine immunogenicity or efficacy against other infections including influenza, Ebola, and yellow fever [16; 17; 18; 19]. Such transcriptomic analysis by our group has also provided a blood-based correlate of risk for TB in humans that continues to be independently validated and is actively progressing toward clinical translation [20; 21; 22].…”

Section: Introductionmentioning

confidence: 99%

Blood Transcriptional Correlates of BCG-Induced Protection Against Tuberculosis in Rhesus Macaques

Liu

Darrah

Zeppa

et al. 2022

Preprint

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Blood-based correlates of vaccine-induced protection against tuberculosis (TB) are urgently needed. We analyzed the blood transcriptome of rhesus macaques immunized with varying doses of intravenous (IV) BCG followed by Mycobacterium tuberculosis (Mtb) challenge. We used high-dose IV BCG recipients for "discovery" and validated our findings in low-dose recipients and in an independent cohort of macaques receiving BCG via different routes. We identified seven vaccine-induced gene modules, including an innate module (module 1) enriched for type 1 interferon and RIG-I-like receptor signaling pathways. Module 1 on day 2 post-vaccination was highly correlated with lung antigen-responsive CD4 T cells at week 8 and with Mtb and granuloma burden following challenge. Parsimonious signatures within module 1 at day 2 post-vaccination predicted protection following challenge with AUROCs >= 0.91. Together these results indicate that the early innate transcriptional response to IV BCG in peripheral blood may provide a robust correlate of protection against TB.

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Are mRNA based transcriptomic signatures ready for diagnosing tuberculosis in the clinic? - A review of evidence and the technological landscape

Cited by 21 publications

References 61 publications

Host Blood Transcriptional Signatures as Candidate Biomarkers for Predicting Progression to Active Tuberculosis

Host Blood Transcriptional Signatures as Candidate Biomarkers for Predicting Progression to Active Tuberculosis

Challenges and the Way forward in Diagnosis and Treatment of Tuberculosis Infection

Blood Transcriptional Correlates of BCG-Induced Protection Against Tuberculosis in Rhesus Macaques

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