Excessive Cytolytic Responses Predict Tuberculosis Relapse After Apparently Successful Treatment.

Cliff, JM; Cho, JE; Lee, JS; Ronacher, K; King, EC; van Helden, P; Walzl, G; Dockrell, HM; (2015) Excessive Cytolytic Responses Predict Tuberculosis Relapse After Apparently Successful Treatment. The Journal of infectious diseases, 213 (3). pp. 485-95. ISSN 0022-1899 DOI: 10.1093/infdis/jiv447

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BACKGROUND: 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.<br/> METHODS: 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.<br/> RESULTS: 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.<br/> CONCLUSIONS: These data show that patients who will subsequently experience relapse exhibit altered immune responses, including excessively robust cytolytic responses to M. tuberculosis in vitro, at the time of diagnosis, compared with patients who will achieve durable cure. Together with microbiological and clinical indices, these differences could be exploited in drug development.<br/>

Item Type: Article
Faculty and Department: Academic Services & Administration > Academic Administration
Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
Research Centre: TB Centre
PubMed ID: 26351358
Web of Science ID: 372436000021
URI: http://researchonline.lshtm.ac.uk/id/eprint/2299121


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