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 metasignature
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 metasignature
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.