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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Identification of biomarkers for tuberculosis disease using a novel dual-color RT-MLPA assay
Genes and Immunity, Volume 13, No. 1, Year 2012
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Description
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. © 2012 Macmillan Publishers Limited All rights reserved.
Authors & Co-Authors
Joosten, Simone A.
Netherlands, Leiden
Leids Universitair Medisch Centrum
Goeman, Jelle J.
Netherlands, Leiden
Leids Universitair Medisch Centrum
Sutherland, Jayne S.
Gambia, Banjul
Medical Research Council Laboratories Gambia
Opmeer, L.
Netherlands, Leiden
Leids Universitair Medisch Centrum
De Boer, K. G.
Netherlands, Leiden
Leids Universitair Medisch Centrum
Jacobsen, Marc
Germany, Berlin
Max Planck Institute for Infection Biology
Germany, Hamburg
Bernhard Nocht Institut Fur Tropenmedizin Hamburg
Kaufmann, Stefan Hugo Ernst
Germany, Berlin
Max Planck Institute for Infection Biology
Finos, Livio
Netherlands, Leiden
Leids Universitair Medisch Centrum
Magis-Escurra, Cécile
Netherlands, Leiden
Leids Universitair Medisch Centrum
Netherlands, Groesbeek
Nijmegen University Medical Center Dekkerswald
Ota, Martin Okechukwu C.
Gambia, Banjul
Medical Research Council Laboratories Gambia
Ottenhoff, Tom H.M.
Netherlands, Leiden
Leids Universitair Medisch Centrum
Haks, Mariëlle C.
Netherlands, Leiden
Leids Universitair Medisch Centrum
Statistics
Citations: 101
Authors: 12
Affiliations: 5
Identifiers
Doi:
10.1038/gene.2011.64
ISSN:
14664879
Research Areas
Cancer
Infectious Diseases
Study Design
Cohort Study
Study Approach
Quantitative