Gene‐Expression Patterns in Whole Blood Identify Subjects at Risk for Recurrent Tuberculosis

Mistry, Rohit; Cliff, Jacqueline M.; Clayton, C. L.; Beyers, Nulda; Mohamed, Yasmin S.; Wilson, Paul; Dockrell, Hazel M.; Wallace, Donald MackenzieHG; Helden, Paul D. van; Duncan, Ken; Lukey, Pauline T.

doi:10.1086/510397

Cited by 128 publications

(95 citation statements)

References 37 publications

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“…[9][10][11][12][13][14]17,18 Several biomarkers identified earlier to discriminate between TB cases and LTBIs in German and South African cohorts (for example, FCGR1A (CD64), LTF and RAB33A), 13,19 were confirmed in the current study cohort from the Gambia. Intriguingly, FCGR1A is the only biomarker from our signature that was also identified by a recent large-scale microarray analysis in UK and South-African TB patients, 16 discriminating active TB disease from LTBI, despite being not specific for TB when compared with other inflammatory diseases.…”

Section: Discussionsupporting

confidence: 78%

Identification of biomarkers for tuberculosis disease using a novel dual-color RT–MLPA assay

et al. 2011

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Owing to our lack of understanding of the factors that constitute protective immunity during natural infection with Mycobacterium tuberculosis (Mtb), there is an urgent need to identify host biomarkers that predict long-term outcome of infection in the absence of therapy. Moreover, the identification of host biomarkers that predict (in)adequate response to tuberculosis (TB) treatment would similarly be a major step forward. To identify/monitor multi-component host biomarker signatures at the transcriptomic level in large human cohort studies, we have developed and validated a dual-color reversetranscriptase multiplex ligation-dependent probe amplification (dcRT-MLPA) method, permitting rapid and accurate expression profiling of as many as 60-80 transcripts in a single reaction. dcRT-MLPA is sensitive, highly reproducible, high-throughput, has an extensive dynamic range and is as quantitative as QPCR. We have used dcRT-MLPA to characterize the human immune response to Mtb in several cohort studies in two genetically and geographically diverse populations. A biomarker signature was identified that is strongly associated with active TB disease, and was profoundly distinct from that associated with treated TB disease, latent infection or uninfected controls, demonstrating the discriminating power of our biomarker signature. Identified biomarkers included apoptosis-related genes and T-cell/B-cell markers, suggesting important contributions of adaptive immunity to TB pathogenesis.

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Section: Discussionsupporting

confidence: 78%

Identification of biomarkers for tuberculosis disease using a novel dual-color RT–MLPA assay

et al. 2011

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“…GSE34608). 1 To whom correspondence may be addressed. E-mail: maertzdorf@mpiib-berlin.mpg.de or kaufmann@mpiib-berlin.mpg.de.…”

Section: Resultsmentioning

confidence: 99%

“…G ene expression in peripheral blood cells from tuberculosis (TB) patients and healthy controls, both latently Mycobacterium tuberculosis-infected and uninfected, has been profiled by several groups in the recent past (1)(2)(3)(4)(5)(6)(7). Identified expression profiles indicate chronic activation of the immune system, with a marked activation of IFN signaling (3), proinflammatory signaling through the JAK-STAT pathway (5,6), and elevated expression of Fc γ-receptors and their downstream response elements (2,4).…”

mentioning

confidence: 99%

Common patterns and disease-related signatures in tuberculosis and sarcoidosis

Maertzdorf

Weiner

Mollenkopf

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

302

308

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In light of the marked global health impact of tuberculosis (TB), strong focus has been on identifying biosignatures. Gene expression profiles in blood cells identified so far are indicative of a persistent activation of the immune system and chronic inflammatory pathology in active TB. Definition of a biosignature with unique specificity for TB demands that identified profiles can differentiate diseases with similar pathology, like sarcoidosis (SARC). Here, we present a detailed comparison between pulmonary TB and SARC, including whole-blood gene expression profiling, microRNA expression, and multiplex serum analytes. Our analysis reveals that previously disclosed gene expression signatures in TB show highly similar patterns in SARC, with a common up-regulation of proinflammatory pathways and IFN signaling and close similarity to TB-related signatures. microRNA expression also presented a highly similar pattern in both diseases, whereas cytokines in the serum of TB patients revealed a slightly elevated proinflammatory pattern compared with SARC and controls. Our results indicate several differences in expression between the two diseases, with increased metabolic activity and significantly higher antimicrobial defense responses in TB. However, matrix metallopeptidase 14 was identified as the most distinctive marker of SARC. Described communalities as well as unique signatures in blood profiles of two distinct inflammatory pulmonary diseases not only have considerable implications for the design of TB biosignatures and future diagnosis, but they also provide insights into biological processes underlying chronic inflammatory disease entities of different etiology.G ene expression in peripheral blood cells from tuberculosis (TB) patients and healthy controls, both latently Mycobacterium tuberculosis-infected and uninfected, has been profiled by several groups in the recent past (1-7). Identified expression profiles indicate chronic activation of the immune system, with a marked activation of IFN signaling (3), proinflammatory signaling through the JAK-STAT pathway (5, 6), and elevated expression of Fc γ-receptors and their downstream response elements (2, 4). Although these biosignatures have been identified by several independent groups and possess the potential to discriminate latently M. tuberculosis-infected healthy individuals from active TB patients, the question remains whether these gene expression signatures are specific for TB or shared, at least in part, with diseases of similar pathology but distinct etiology.To address this question, we have conducted a comparative analysis of blood profiles in patients with active pulmonary disease manifestation of TB and sarcoidosis (SARC). The rational for choosing pulmonary SARC for such a comparison is the remarkable similarity in immune activation with active TB, suggesting a shared underlying pathophysiology (8). Although SARC is generally considered a noncommunicable disease of unknown etiology, patients with pulmonary involvement present with histological and ...

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“…These studies mostly relied on peripheral blood samples from patients with active ( pulmonary) TB disease directly after diagnosis and contrasted gene expression profiles to those of healthy (infected) controls or patients with other inflammatory/pulmonary disorders (Jacobsen et al 2007;Mistry et al 2007;Berry et al 2010;Maertzdorf et al 2011aMaertzdorf et al ,b, 2012Bloom et al 2013;Cliff et al 2013;Kaforou et al 2013). Each individual study performed extensive data analysis to identify key signatures that could discriminate TB disease from the respective control group(s).…”

Section: Transcriptomic Approaches To Tb Biomarker Discovery a Meta-lmentioning

confidence: 99%

Clinical Immunology and Multiplex Biomarkers of Human Tuberculosis

Walzl

Haks

Joosten

et al. 2014

Cold Spring Harbor Perspectives in Medicine

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Gene‐Expression Patterns in Whole Blood Identify Subjects at Risk for Recurrent Tuberculosis

Abstract: A simple test based on gene-expression patterns may be used as a biomarker of cure while identifying patients who are at risk for relapse. This would facilitate the introduction of new tuberculosis drugs.

Cited by 128 publications

References 37 publications

Identification of biomarkers for tuberculosis disease using a novel dual-color RT–MLPA assay

Identification of biomarkers for tuberculosis disease using a novel dual-color RT–MLPA assay

Common patterns and disease-related signatures in tuberculosis and sarcoidosis

Clinical Immunology and Multiplex Biomarkers of Human Tuberculosis

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