Identification of biomarkers for tuberculosis disease using a novel dual-color RT-MLPA assay
| Autor: | Marc Jacobsen, Simone A. Joosten, Lizet Opmeer, Jayne S. Sutherland, Martin O. C. Ota, Livio Finos, Cecile Magis-Escurra, Tom H. M. Ottenhoff, Mariëlle C. Haks, K. G. de Boer, Jelle J. Goeman, Stefan H. E. Kaufmann |
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| Rok vydání: | 2012 |
| Předmět: |
Genetic Markers
Tuberculosis dcRT-MLPA host biomarkers Immunology Disease Biology Real-Time Polymerase Chain Reaction Sensitivity and Specificity Mycobacterium tuberculosis 03 medical and health sciences 0302 clinical medicine Genetics medicine Humans Multiplex Multiplex ligation-dependent probe amplification Genetics (clinical) 030304 developmental biology 0303 health sciences Gene Expression Profiling Poverty-related infectious diseases [N4i 3] Reproducibility of Results medicine.disease Acquired immune system biology.organism_classification 3. Good health Gene expression profiling tuberculosis Biomarker (medicine) Nucleic Acid Amplification Techniques 030215 immunology |
| Zdroj: | Genes and Immunity, 13, 71-82 Genes and Immunity Genes and Immunity; Vol 13 Genes and Immunity, 13(1), 71-82 Genes and Immunity, 13, 1, pp. 71-82 |
| ISSN: | 1466-4879 |
| Popis: | 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.Genes and Immunity advance online publication, 29 September 2011; doi:10.1038/gene.2011.64. |
| Databáze: | OpenAIRE |
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