Gene-expression patterns in whole blood identify subjects at risk for recurrent tuberculosis

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dc.contributor.authorMistry R.
dc.contributor.authorCliff J.M.
dc.contributor.authorClayfon C.L.
dc.contributor.authorBeyers N.
dc.contributor.authorMohamed Y.S.
dc.contributor.authorWilson P.A.
dc.contributor.authorDockrell H.M.
dc.contributor.authorWallace D.M.
dc.contributor.authorVan Helden P.D.
dc.contributor.authorDuncan K.
dc.contributor.authorLukey P.T.
dc.date.accessioned2011-05-15T16:03:34Z
dc.date.available2011-05-15T16:03:34Z
dc.date.issued2007
dc.description.abstractBackground. The majority of patients with tuberculosis who comply with appropriate treatment are cured. However, ∼5% subsequently have a repeat disease episode, usually within 2 years of successful combination therapy. Presently, there is no way of predicting which patients will experience a relapse. Methods. We identified 10 subjects who had previously experienced recurrent tuberculosis and carefully matched them to cured subjects who had had only 1 episode of tuberculosis, to patients with active tuberculosis, and to latently infected healthy subjects. We compared their ex vivo whole-blood gene-expression profiles by use of DNA array technology and confirmed the results by use of quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). Results. The 4 clinical tuberculosis groups exhibited distinct patterns of gene expression. The gene-transcript profiles of the patients with recurrent tuberculosis were more similar to those of the patients with active tuberculosis than to those of the cured or latently infected subjects. Discriminant analysis of a training data set showed that 9 genes were sufficient to classify the subjects. We confirmed that measurement of the expression of these genes by qRT-PCR can accurately discriminate between subjects in a test set of samples. Conclusions. 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. © 2006 by the Infectious Diseases Society of America. All rights reserved.
dc.description.versionArticle
dc.identifier.citationJournal of Infectious Diseases
dc.identifier.citation195
dc.identifier.citation3
dc.identifier.issn221899
dc.identifier.urihttp://hdl.handle.net/10019.1/12677
dc.subjectbiological marker
dc.subjectethambutol
dc.subjectisoniazid
dc.subjectpyrazinamide
dc.subjectrifampicin
dc.subjectaccuracy
dc.subjectarticle
dc.subjectclinical article
dc.subjectcombination chemotherapy
dc.subjectdiscriminant analysis
dc.subjectDNA microarray
dc.subjectgene expression profiling
dc.subjecthigh risk patient
dc.subjecthuman
dc.subjectnonhuman
dc.subjectnucleotide sequence
dc.subjectpriority journal
dc.subjectquantitative analysis
dc.subjectrecurrent infection
dc.subjectrelapse
dc.subjectreverse transcription polymerase chain reaction
dc.subjecttreatment outcome
dc.subjecttuberculosis
dc.subjectunindexed sequence
dc.subjectBiological Markers
dc.subjectBlood Cells
dc.subjectDisease Progression
dc.subjectGene Expression Profiling
dc.subjectHumans
dc.subjectPolymerase Chain Reaction
dc.subjectProteins
dc.subjectRecurrence
dc.subjectRNA, Messenger
dc.subjectSuppressor of Cytokine Signaling Proteins
dc.subjectTuberculosis
dc.titleGene-expression patterns in whole blood identify subjects at risk for recurrent tuberculosis
dc.typeArticle
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