期刊
PLOS ONE
卷 11, 期 10, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0162220
关键词
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资金
- Francis Crick Institute
- Cancer Research UK [FC001126]
- U.K. Medical Research Council [FC001126]
- Wellcome Trust [FC001126]
- UK Medical Research Council (MRC)
- UK Department for International Development (DFID) under the MRC/DFID [MR/J010723/1]
- Department of Health via the National Institutes of Health Research comprehensive Biomedical Research Centre
- King's College London
- SILA
- MRC [MC_U117565642, MR/J010723/1] Funding Source: UKRI
- Cancer Research UK
- The Francis Crick Institute [10126] Funding Source: researchfish
- Medical Research Council [1365570, MR/J010723/1, MC_U117565642, 1105853] Funding Source: researchfish
- The Francis Crick Institute [10127] Funding Source: researchfish
Background Mycobacterium tuberculosis infection is a leading cause of infectious death worldwide. Gene-expression microarray studies profiling the blood transcriptional response of tuberculosis (TB) patients have been undertaken in order to better understand the host immune response as well as to identify potential biomarkers of disease. To date most of these studies have focused on pulmonary TB patients with gene-expression profiles of extra-pulmonary TB patients yet to be compared to those of patients with pulmonary TB or sarcoidosis. Methods A novel cohort of patients with extra-pulmonary TB and sarcoidosis was recruited and the transcriptional response of these patients compared to those with pulmonary TB using a variety of transcriptomic approaches including testing a previously defined 380 gene meta-signature of active TB. Results The 380 meta-signature broadly differentiated active TB from healthy controls in this new dataset consisting of pulmonary and extra-pulmonary TB. The top 15 genes from this meta-signature had a lower sensitivity for differentiating extra-pulmonary TB from healthy controls as compared to pulmonary TB. We found the blood transcriptional responses in pulmonary and extra-pulmonary TB to be heterogeneous and to reflect the extent of symptoms of disease. Conclusions The transcriptional signature in extra-pulmonary TB demonstrated heterogeneity of gene expression reflective of symptom status, while the signature of pulmonary TB was distinct, based on a higher proportion of symptomatic individuals. These findings are of importance for the rational design and implementation of mRNA based TB diagnostics.
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