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E-GEOD-36238 - Tuberculosis Patients Blood Gene Expression Through Treatment (cured and end-of-treatment patients)

Status
Released on 9 August 2012, last updated on 20 August 2012
Organism
Homo sapiens
Samples (18)
Array (1)
Protocols (8)
Description
Background Accurate assessment of treatment efficacy would facilitate clinical trials of new anti-tuberculosis drugs. TB patients exhibit altered peripheral immunity which reverts during successful treatment. We hypothesised that these changes could be observed in whole blood transcriptome profiles. Methods Ex vivo blood samples from 27 pulmonary TB patients were assayed at diagnosis and during conventional treatment. RNA was processed and hybridised to Affymetrix GeneChips, to determine expression of over 47,000 transcripts. Findings There were significant changes in expression of over 4,000 genes during treatment. Rapid, large scale changes were detected, with down-regulated expression of ~1,000 genes within the first week, including inflammatory markers such as the complement components C1q and C2. This was followed by slower changes in expression of different networks of genes, including a later increase in expression of B cell markers, transcription factors and signalling molecules. Interpretation The expression of many genes is drastically altered during TB disease, with components of the humoral immune response being markedly affected. The treatment-induced restoration reflects the simultaneous suppression and activation of different immune responses in TB. The rapid initial down-regulation of expression of inflammatory mediators coincides with rapid killing of actively dividing bacilli, whereas slower delayed changes occur as drugs act on dormant bacilli and as lung pathology resolves. Measurement of biosignatures during clinical trials of new drugs could be useful predictors of rapid bactericidal or sterilizing drug activity. Ex vivo blood samples analysed during TB treatment. These samples are from 9 successfully cured patients at diagnosis and end-of-treatment at 26 weeks.
Experiment type
transcription profiling by array 
Contacts
Jackie Cliff <jackie.cliff@lshtm.ac.uk>, Elizabeth C King, Gerhard Walzl, Hazel M Dockrell, Jacqueline M Cliff, Jang-Eun Cho, Ji-Sook Lee, Katharina Ronacher, Ken Duncan, Nicholas Constantinou, Paul D Van Helden, Pauline T Lukey, Taane G Clark
Citation
Distinct phases of blood gene expression pattern through tuberculosis treatment reflect modulation of the humoral immune response. Cliff JM, Lee JS, Constantinou N, Cho JE, Clark TG, Ronacher K, King EC, Lukey PT, Duncan K, Van Helden PD, Walzl G, Dockrell HM. , PMID:22872737
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-36238.idf.txt
Sample and data relationshipE-GEOD-36238.sdrf.txt
Raw data (1)E-GEOD-36238.raw.1.zip
Processed data (1)E-GEOD-36238.processed.1.zip
Array designA-AFFY-44.adf.txt
R ExpressionSetE-GEOD-36238.eSet.r
Links