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

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 identificat...

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Bibliographic Details
Published in:Genes and immunity Vol. 13; no. 1; pp. 71 - 82
Main Authors: Joosten, S A, Goeman, J J, Sutherland, J S, Opmeer, L, de Boer, K G, Jacobsen, M, Kaufmann, S H E, Finos, L, Magis-Escurra, C, Ota, M O C, Ottenhoff, T H M, Haks, M C
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 01.01.2012
Nature Publishing Group
Subjects:
Adaptive immunity
Apoptosis
Biological markers
Biomarkers
Biomedical and Life Sciences
Biomedicine
Cancer Research
Cohort analysis
Diagnosis
Gene Expression
Gene Expression Profiling
Genes
Genetic Markers - genetics
Human Genetics
Humans
Identification
Immune response
Immune system
Immunology
Infections
Infectious diseases
Latent infection
Lymphocytes B
Lymphocytes T
Mycobacterium tuberculosis
Nucleic Acid Amplification Techniques - methods
original-article
Physiological aspects
Polymerase chain reaction
Real-Time Polymerase Chain Reaction - methods
Reproducibility of Results
Sensitivity and Specificity
Transcriptomics
Tuberculosis
Tuberculosis - genetics
Tuberculosis - immunology
Vaccines
Netherlands
Gambia
dcRT–MLPA
tuberculosis
host biomarkers
ISSN:1466-4879, 1476-5470, 1476-5470
Online Access:Get full text
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Summary: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 reverse-transcriptase 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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ISSN:1466-4879
1476-5470
1476-5470
DOI:10.1038/gene.2011.64