Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Distinct phases of blood gene expression pattern through tuberculosis treatment reflect modulation of the humoral immune response
Journal of Infectious Diseases, Volume 207, No. 1, Year 2013
Notification
URL copied to clipboard!
Description
Background. Accurate assessment of treatment efficacy would facilitate clinical trials of new antituberculosis drugs. We hypothesized that early alterations in peripheral immunity could be measured by gene expression profiling in tuberculosis patients undergoing successful conventional combination treatment. Methods. Ex vivo blood samples from 27 pulmonary tuberculosis patients were assayed at diagnosis and during treatment. RNA was processed and hybridized to Affymetrix GeneChips, to determine expression of over 47 000 transcripts. Results. There were significant ≥2-fold changes in expression of >4000 genes during treatment. Rapid, largescale changes were detected, with down-regulated expression of 1261 genes within the first week, including inflammatory markers such as 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 signaling molecules. Conclusions. The fast initial down-regulation of expression of inflammatory mediators coincided with rapid killing of actively dividing bacilli, whereas slower delayed changes occurred as drugs acted on dormant bacilli and coincided with lung pathology resolution. Measurement of biosignatures during clinical trials of new drugs could be useful predictors of rapid bactericidal or sterilizing drug activity, and would expedite the licensing of new treatment regimens. © The Author 2012.
Authors & Co-Authors
Cliff, Jacqueline Margaret
United Kingdom, London
London School of Hygiene & Tropical Medicine
Lee, Jisook
United Kingdom, London
London School of Hygiene & Tropical Medicine
Clark, Taane Gregory
United Kingdom, London
London School of Hygiene & Tropical Medicine
Ronacher, Katharina
Unknown Affiliation
King, Elizabeth C.
United Kingdom, London
London School of Hygiene & Tropical Medicine
Lukey, Pauline T.
United Kingdom, Brentford
Glaxosmithkline Plc.
Duncan, Ken
Unknown Affiliation
Van Helden, Paul D.
Unknown Affiliation
Walzl, Gerhard
Unknown Affiliation
Dockrell, Hazel M.
United Kingdom, London
London School of Hygiene & Tropical Medicine
Statistics
Citations: 181
Authors: 10
Affiliations: 3
Identifiers
Doi:
10.1093/infdis/jis499
ISSN:
00221899
Research Areas
Genetics And Genomics