p50-associated Cyclooxygenase-2 Extragenic RNA (PACER) and Long Non-coding RNA 13 (LNC13) as potential biomarkers for monitoring tuberculosis treatment (original) (raw)
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Frontiers in Tropical Diseases
Early diagnosis is crucial in controlling tuberculosis globally and in developing countries with the emergence of drug-resistant Mycobacterium tuberculosis strains. Long non-coding RNAs (lncRNAs) are promising tuberculosis diagnostic biomarkers. Two lncRNA diagnostic markers, lncRNA THRIL and lincRNA-p21, were studied as tuberculosis diagnostic biomarkers. This cross-sectional study was conducted at the Center of Respiratory Diseases of LAQUINTINIE hospital and the National Veterinary Laboratory of Douala from December 2020 to August 2021. The ability of lncRNAs to distinguish between 19 healthy controls, 15 latent tuberculosis, and 21 active tuberculosis was estimated using quantitative polymerase chain reaction and Receiver Operating Characteristic curve analysis. Our analysis showed that lncRNA THRIL and lincRNA-p21 were significantly upregulated (P <0.05) in active and latent tuberculosis compared with healthy controls. LincRNA-p21 expression was significantly increased (P &l...
A blood RNA signature for tuberculosis disease risk: a prospective cohort study
Lancet (London, England), 2016
Identification of blood biomarkers that prospectively predict progression of Mycobacterium tuberculosis infection to tuberculosis disease might lead to interventions that combat the tuberculosis epidemic. We aimed to assess whether global gene expression measured in whole blood of healthy people allowed identification of prospective signatures of risk of active tuberculosis disease. In this prospective cohort study, we followed up healthy, South African adolescents aged 12-18 years from the adolescent cohort study (ACS) who were infected with M tuberculosis for 2 years. We collected blood samples from study participants every 6 months and monitored the adolescents for progression to tuberculosis disease. A prospective signature of risk was derived from whole blood RNA sequencing data by comparing participants who developed active tuberculosis disease (progressors) with those who remained healthy (matched controls). After adaptation to multiplex quantitative real-time PCR (qRT-PCR), ...
Host blood RNA signatures predict the outcome of tuberculosis treatment
Tuberculosis, 2017
Biomarkers for tuberculosis treatment outcome will assist in guiding individualized treatment and evaluation of new therapies. To identify candidate biomarkers, RNA sequencing of whole blood from a well-characterized TB treatment cohort was performed. Application of a validated transcriptional correlate of risk for TB revealed symmetry in host gene expression during progression from latent TB infection to active TB disease and resolution of disease during treatment, including return to control levels after drug therapy. The symmetry was also seen in a TB disease signature, constructed from the TB treatment cohort, that also functioned as a strong correlate of risk. Both signatures identified patients at risk of treatment failure 1e4 weeks after start of therapy. Further mining of the transcriptomes revealed an association between treatment failure and suppressed expression of mitochondrial genes before treatment initiation, leading to development of a novel baseline (pre-treatment) signature of treatment failure. These novel host responses to TB treatment were integrated into a five-gene real-time PCR-based signature that captures the clinically relevant responses to TB treatment and provides a convenient platform for stratifying patients according to their risk of treatment failure. Furthermore, this 5-gene signature is shown to correlate with the pulmonary inflammatory state (as measured by PET-CT) and can complement sputum-based Gene Xpert for patient stratification, providing a rapid and accurate alternative to current methods.
Micro-RNA: A potential screening marker for latent tuberculosis
IP International Journal of Medical Microbiology and Tropical Diseases, 2023
Abstract An ancient disease, Tuberculosis is one of the most challenging infectious disease contributing to mortality and morbidity worldwide. Tuberculosis elimination globally, by 2050, is a mammoth task as Mycobacterial infections have wide range of presentation, from the clinical to the subclinical or latent and pose a diagnostic and therapeutic challenge. The virulence as well as evading property of Mycobacterium tuberculosisMtb) from the host's immune system confers upon it the ability to remain latent in the host cells. This forms the basis of classification of tuberculosis patient as having latent-TBI or active TB. This review focuses on the role of miRNA as biomarkers of LTBI. The aim is to have an overview of the current knowledge about miRNA, its involvement in TB pathogenesis and its role as a reliable tool for diagnosis of latent tuberculosis. miRNA are non-encoding endogenous RNAs which regulate gene expression by directing their target RNA for degradation or translational repression. Degraded RNA are released in the extracellular milieu, are present in various body fluids, such as blood, saliva, and urine, and are biomarkers for a number of diseases including cancer, Parkinsons’ disease, CAD, liver diseases, TB and other infectious diseases. miRNAs are differentially expressed during active TB and LTBI, and therefore can be used as biomarkers of disease progression and response to anti-TB therapy. This will further permit more specific therapeutic interventions in TB management. A thorough search of available literature resources was performed on online databases such as Google Scholar, NCBI, Nature, Research gate, PubMed, Science Direct. It was found that miRNA are promising biomarkers to identify healthy latent TB individuals for further course of action and can be reliable tools for routine use in current clinical practice for specific therapeutic interventions to limit active TB population. They meet the criteria of ideal biomarkers, such as minimally invasive, accessibility, high specificity, and sensitivity. Keywords: Biomarkers, Latent tuberculosis, miRNA, Pediatric, Diagnosis
mBio
In tuberculosis (TB), as in other infectious diseases, studies of small noncoding RNAs (sncRNA) in peripheral blood have focused on microRNAs (miRNAs) but have neglected the other major sncRNA classes in spite of their potential functions in host gene regulation. Using RNA sequencing of whole blood, we have therefore determined expression of miRNA, PIWI-interacting RNA (piRNA), small nucleolar RNA (snoRNA), and small nuclear RNA (snRNA) in patients with TB (n = 8), latent TB infection (LTBI; n = 21), and treated LTBI (LTBItt; n = 6) and in uninfected exposed controls (ExC; n = 14). As expected, sncRNA reprogramming was greater in TB than in LTBI, with the greatest changes seen in miRNA populations. However, substantial dynamics were also evident in piRNA and snoRNA populations. One miRNA and 2 piRNAs were identified as moderately accurate (area under the curve [AUC] = 0.70 to 0.74) biomarkers for LTBI, as were 1 miRNA, 1 piRNA, and 2 snoRNAs (AUC = 0.79 to 0.91) for accomplished LTB...
BackgroundUndiagnosed tuberculosis (TB) remains a major threat for people living with HIV (PLHIV). Multiple blood transcriptomic biomarkers have shown promise for TB diagnosis. We sought to evaluate their diagnostic accuracy and clinical utility for systematic pre-antiretroviral therapy (ART) TB screening.MethodsWe enrolled consecutive adults referred to start ART at a community health centre in Cape Town, South Africa, irrespective of symptoms. Sputa were obtained (using induction if required) for two liquid cultures. Whole-blood RNA samples underwent transcriptional profiling using a custom Nanostring gene-panel. We measured the diagnostic accuracy of seven candidate RNA biomarkers for the reference standard ofMycobacterium tuberculosisculture status, using area under the receiver-operating characteristic curve (AUROC) analysis, and sensitivity/specificity at pre-specified thresholds (two standard scores above the mean of healthy controls; Z2). Clinical utility was assessed using ...
Journal of Cellular and Molecular Medicine, 2017
Technological advances in RNA biology greatly improved transcriptome profiling during the last two decades. Besides the discovery of many small RNAs (sRNA) that are involved in the physiological and pathophysiological regulation of various cellular circuits, it becomes evident that the corresponding RNA genes might also serve as potential biomarkers to monitor the progression of disease and treatment. sRNA gene candidate npcTB_6715 was previously identified via experimental RNomic (unpublished data), and we report its application as potential biomarker for the detection of Mycobacterium tuberculosis (MTB) in patient samples. For proof of principle, we developed a multiplex PCR assay and report its validation with 500 clinical cultures, positive for Mycobacteria. The analysis revealed 98.9% sensitivity, 96.1% specificity, positive and negative predictive values of 98.6% and 96.8%, respectively. These results underscore the diagnostic value of the sRNA gene as diagnostic marker for the specific detection of MTB in clinical samples. Its successful application and the general ease of PCR-based detection compared to standard bacterial culture techniques might be the first step towards 'point-of-care' diagnostics of Mycobacteria. To the best of our knowledge, this is the first time for the design of diagnostic applications based on sRNA genes, in Mycobacteria.
Clinical Microbiology and Infection, 2012
Mycobacterium tuberculosis m-RNA quantitation in sputum of pulmonary tuberculosis patients before starting supervised treatment was evaluated as a surrogate for response. Sputum specimens were collected from 50 patients (DOTS category II treatment; 303 specimens, day 0 to fourth month) and 16 controls (non-tubercular lung disorders). Microscopy, reverse-transcriptase PCR and DNA-PCR were compared with culture using the BACTEC 460 system. TaqMan real-time RT-PCR quantitated the mRNA levels. RT-PCR (sensitivity, 10 organisms/mL) and culture results were concordant. mRNA declined with time and correlated with culture clearance. Thirty-nine (78%) patients were smear, culture and RT-PCR negative at 2 months of treatment. Day 0 mRNA levels had statistically significant correlation with time to culture conversion and drug resistance (p 0.041). Of seven patients with sensitive isolates but high m-RNA levels, four presented with re-infection/mixed infection later, while three presented with relapse (ninth to twentieth month). The control group specimens were negative for the above tests. M. tuberculosis mRNA in the sputum is a useful prognostic marker and its quantitation an early and reliable indicator for monitoring response, prediction of culture conversion, drug resistance, re-infection and relapse. mRNA quantitation may prove to be of great value for evaluating the response to new drugs under trial.
Communications Medicine
Background Sensitive point-of-care screening tests are urgently needed to identify individuals at highest risk of tuberculosis. We prospectively tested performance of host-blood transcriptomic tuberculosis signatures. Methods Adults without suspicion of tuberculosis were recruited from five endemic South African communities. Eight parsimonious host-blood transcriptomic tuberculosis signatures were measured by microfluidic RT-qPCR at enrolment. Upper respiratory swab specimens were tested with a multiplex bacterial-viral RT-qPCR panel in a subset of participants. Diagnostic and prognostic performance for microbiologically confirmed prevalent and incident pulmonary tuberculosis was tested in all participants at baseline and during active surveillance through 15 months follow-up, respectively. Results Among 20,207 HIV-uninfected and 963 HIV-infected adults screened; 2923 and 861 were enroled. There were 61 HIV-uninfected (weighted prevalence 1.1%) and 10 HIV-infected (prevalence 1.2%) ...