Excessive Cytolytic Responses Predict Tuberculosis Relapse After Apparently Successful Treatment

The Journal of Infectious Diseases
Jacqueline M CliffHazel M Dockrell

Abstract

Currently, there are no tools to accurately predict tuberculosis relapse. This study aimed to determine whether patients who experience tuberculosis relapse have different immune responses to mycobacteria in vitro than patients who remain cured for 2 years. Patients with an initial episode of pulmonary tuberculosis were recruited in South Africa. Diluted blood, collected at diagnosis and after 2 and 4 weeks of treatment, was cultured with live Mycobacterium tuberculosis for 6 days, and cellular RNA was frozen. Gene expression in samples from 10 patients who subsequently experienced relapse, confirmed by strain genotyping, was compared to that in samples from patients who remained cured, using microarrays. At diagnosis, expression of 668 genes was significantly different in samples from patients who experienced relapse, compared with expression in patients who remained successfully cured; these differences persisted for at least 4 weeks. Gene ontology and biological pathways analyses revealed significant upregulation of genes involved in cytotoxic cell-mediated killing. Results were confirmed by real-time quantitative reverse-transcription polymerase chain reaction analysis in a wider patient cohort. These data show that patient...Continue Reading

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Citations

Apr 1, 2016·Expert Review of Respiratory Medicine·Neesha RockwoodRobert J Wilkinson
Mar 11, 2016·Pathogens and Disease·Hazel M Dockrell
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