Latent Tuberculosis Infection Diagnosis among Household Contacts in a High Tuberculosis-Burden Area: a Comparison between Transcript Signature and Interferon Gamma Release Assay

Kaul, Sheetal; Nair, Vivek; Birla, Shweta; Dhawan, Shikha; Rathore, Sumit; Khanna, Vishal; Lohiya, Sheelu; Ali, Shakir; Mannan, Shamim; Rade, Kirankumar; Malhotra, Pawan; Gupta, Dinesh; Khanna, Ashwani; Mohmmed, Asif

doi:10.1128/spectrum.02445-21

Cited by 8 publications

(7 citation statements)

References 34 publications

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“…Furthermore, similar low expression levels in TBEx IGRA negative individuals as in LTBI individuals suggests that IGRA test is underdiagnosing LTBI among TB exposed participants. No prior study has speci cally evaluated this phenomenon, although Kaul et al 20 showed no differences in expression for ASUN, NEMF and GBP5, genes that we also evaluated, among IGRA positive vs IGRA negative household contacts in India. The control group used in the Indian cohort were exposed household IGRA negative individuals and their assay diagnostic performance was very low for a combination of markers 20 .…”

Section: Discussionmentioning

confidence: 64%

Suppression of host gene expression is associated with latent TB infection: a possible diagnostic biomarker

Nakiboneka,

Margaritella,

Nyirenda

et al. 2024

Preprint

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The World Health Organization End TB strategy aims for a 90% reduction of tuberculosis (TB) incidence by 2035. Systematic testing and treatment of latent TB infection (LTBI) among contacts of active TB (ATB) patients is recommended as one of the ways to curtail TB incidence. However, there is a shortage of tools to accurately diagnose LTBI. We assessed the appropriateness of whole blood host transcriptomic markers (TM) to diagnose LTBI among household contacts of bacteriologically confirmed index cases compared to HIV negative healthy controls (HC). QuantiFERON-TB Gold Plus Interferon gamma release assay (IGRA) and reverse-transcriptase quantitative PCR were used to determine LTBI and quantify TM expression respectively. Association between TM expression and LTBI was evaluated by logistic regression modelling. A total of 100 participants, 49 TB exposed (TBEx) household contacts and 51 HC, were enrolled. Twenty-five (51%) TBEx individuals tested positive by IGRA, and were denoted as LTBI individuals, and 37 (72.5%) HC were IGRA-negative. Expression of 11 evaluated TM was significantly suppressed among LTBI compared to HC. Out of the 11 TM, ZNF296 and KLF2 expressions were strongly associated with LTBI and successfully differentiated LTBI from HC. Paradoxically, 21 (49%) TBEx participants who tested IGRA negative exhibited the same pattern of suppressed TM expression as IGRA positive (LTBI-confirmed individuals). Results suggest suppression of gene expression underlies LTBI and may be a more sensitive diagnostic biomarker than standard-of-care IGRA.

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Section: Discussionmentioning

confidence: 64%

Suppression of host gene expression is associated with latent TB infection: a possible diagnostic biomarker

Nakiboneka,

Margaritella,

Nyirenda

et al. 2024

Preprint

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“…GBP5 activates NLRP3 in ammatory vesicle assembly and elicits an in ammatory response to pathogenic bacteria, playing a role in innate immunity and in ammation. Some studies have reported signi cantly increased expression of the GBP5 gene and protein in whole blood of patients with active tuberculosis (19,20). However, no relevant reports on GBP5 in extrapulmonary TB.…”

Section: Discussionmentioning

confidence: 99%

“…A study found by quantitative real-time polymerase chain reaction (qPCR) technique that FCGR1B gene expression was positively correlated with bacterial load and C-reactive protein in TB patients and also showed good diagnostic power in EPTB (35). One study identi ed a multigene mRNA combination containing the FCGR1B gene as a potential molecular marker for the diagnosis of active tuberculosis (19). FCGR1B may serve as a potential molecular marker for EPTB.…”

Section: Discussionmentioning

confidence: 99%

Screening of extra-pulmonary tuberculosis signature genes and analysis of correlation with immune cells

Romani

Liu

et al. 2023

Preprint

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Extrapulmonary tuberculosis (EPTB) is characterized by atypical clinical symptoms, difficulty in diagnosis, a high rate of disability, and a high mortality rate. Early EPTB diagnosis aids recovery. The gold standard for EPTB diagnosis needs surgery, puncture, and other invasive testing to collect a lesion sample for mycobacterium tuberculosis culture and Xpert. However, early diagnosis of EPTB has been challenging due to the lack of specificity and inability of current diagnostic methods to differentiate between active and latent EPTB infections. As a result, there is an urgent clinical need to develop new methods to improve the early detection of EPTB. In this study, we employed bioinformatics and machine learning methods to identify EPTB hallmark genes. Furthermore, we looked at the relationship between these genes and immune cell infiltration. We obtained 97 differentially expressed genes (DEGs) from the analysis. The genes were split into 14 modules by weighted gene co-expression network analysis (WGCNA). Six of the intersecting genes, GBP5, UBE2L6, IFITM3, SERPING1, C1QB, and FCGR1B, were identified as EPTB hub genes at final screening using the last absolute shrinkage and selection operator (LASSO) and random Forest. The presence of some immune cells in EPTB correlated with the expression of these genes.

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“…Until now, the diagnosis confirmation of LTBI patients still followed the results of the IGRA test (Herrera et al, 2011). Nevertheless, several limitations, such as the large amount of blood needed, limited assay reproducibility, low sensitivity, unknown prognostic value, and slow sample processing, have limited IGRA usage for mass testing (Herrera et al, 2011;Kaul et al, 2022). A recent publication confirmed FCGR1B, GBP1, and GBP5 as the transcript signatures that distinguished between LTB1 and active TB, which could be helpful in screening LTBI on a mass scale (Kaul et al, 2022).…”

Section: Tb Management Benefits From the Utilization Of Immune Biomar...mentioning

confidence: 99%

“…Nevertheless, several limitations, such as the large amount of blood needed, limited assay reproducibility, low sensitivity, unknown prognostic value, and slow sample processing, have limited IGRA usage for mass testing (Herrera et al, 2011;Kaul et al, 2022). A recent publication confirmed FCGR1B, GBP1, and GBP5 as the transcript signatures that distinguished between LTB1 and active TB, which could be helpful in screening LTBI on a mass scale (Kaul et al, 2022). Furthermore, they classified the LTBI into clusters following the IFN-g values in TB1 and TB2 antigens using machine-learning cluster analysis.…”

Section: Tb Management Benefits From the Utilization Of Immune Biomar...mentioning

confidence: 99%

Advancing personalized medicine for tuberculosis through the application of immune profiling

Thu

Dat²,

Jayanti³

et al. 2023

Front. Cell. Infect. Microbiol.

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While early and precise diagnosis is the key to eliminating tuberculosis (TB), conventional methods using culture conversion or sputum smear microscopy have failed to meet demand. This is especially true in high-epidemic developing countries and during pandemic-associated social restrictions. Suboptimal biomarkers have restricted the improvement of TB management and eradication strategies. Therefore, the research and development of new affordable and accessible methods are required. Following the emergence of many high-throughput quantification TB studies, immunomics has the advantages of directly targeting responsive immune molecules and significantly simplifying workloads. In particular, immune profiling has been demonstrated to be a versatile tool that potentially unlocks many options for application in TB management. Herein, we review the current approaches for TB control with regard to the potentials and limitations of immunomics. Multiple directions are also proposed to hopefully unleash immunomics’ potential in TB research, not least in revealing representative immune biomarkers to correctly diagnose TB. The immune profiles of patients can be valuable covariates for model-informed precision dosing-based treatment monitoring, prediction of outcome, and the optimal dose prediction of anti-TB drugs.

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Latent Tuberculosis Infection Diagnosis among Household Contacts in a High Tuberculosis-Burden Area: a Comparison between Transcript Signature and Interferon Gamma Release Assay

Cited by 8 publications

References 34 publications

Suppression of host gene expression is associated with latent TB infection: a possible diagnostic biomarker

Suppression of host gene expression is associated with latent TB infection: a possible diagnostic biomarker

Screening of extra-pulmonary tuberculosis signature genes and analysis of correlation with immune cells

Advancing personalized medicine for tuberculosis through the application of immune profiling

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