Open Access Research article

Combination of gene expression patterns in whole blood discriminate between tuberculosis infection states

Adane Mihret12*, Andre G Loxton3, Yonas Bekele1, Stefan HE Kaufmann4, Martin Kidd5, Mariëlle C Haks6, Tom HM Ottenhoff6, Abraham Aseffa1, Rawleigh Howe1 and Gerhard Walzl3

Author Affiliations

1 Armauer Hansen Research Institute, Addis Ababa, Ethiopia

2 Department of Microbiology, Immunology and Parasitology, School of Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia

3 Division of Molecular Biology and Human Genetics, DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, MRC Centre for Molecular and Cellular Biology, Faculty of Medicine and Health Sciences, Stellenbosch University, Francie van Zijl Drive, P.O. Box 19063, 7505 Tygerberg, South Africa

4 Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany

5 Centre for Statistical Consultation, Department of Statistics and Actuarial Sciences, University of Stellenbosch, Stellenbosch, South Africa

6 Department of Infectious Diseases, Leiden University Medical Centre, Leiden, The Netherlands

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BMC Infectious Diseases 2014, 14:257  doi:10.1186/1471-2334-14-257

Published: 13 May 2014

Abstract

Background

Genetic factors are involved in susceptibility or protection to tuberculosis (TB). Apart from gene polymorphisms and mutations, changes in levels of gene expression, induced by non-genetic factors, may also determine whether individuals progress to active TB.

Methods

We analysed the expression level of 45 genes in a total of 47 individuals (23 healthy household contacts and 24 new smear-positive pulmonary TB patients) in Addis Ababa using a dual colour multiplex ligation-dependent probe amplification (dcRT-MLPA) technique to assess gene expression profiles that may be used to distinguish TB cases and their contacts and also latently infected (LTBI) and uninfected household contacts.

Results

The gene expression level of BLR1, Bcl2, IL4d2, IL7R, FCGR1A, MARCO, MMP9, CCL19, and LTF had significant discriminatory power between sputum smear-positive TB cases and household contacts, with AUCs of 0.84, 0.81, 0.79, 0.79, 0.78, 0.76, 0.75, 0.75 and 0.68 respectively. The combination of Bcl2, BLR1, FCGR1A, IL4d2 and MARCO identified 91.66% of active TB cases and 95.65% of household contacts without active TB. The expression of CCL19, TGFB1, and Foxp3 showed significant difference between LTBI and uninfected contacts, with AUCs of 0.85, 0.82, and 0.75, respectively, whereas the combination of BPI, CCL19, FoxP3, FPR1 and TGFB1 identified 90.9% of QFT- and 91.6% of QFT+ household contacts.

Conclusions

Expression of single and especially combinations of host genes can accurately differentiate between active TB cases and healthy individuals as well as between LTBI and uninfected contacts.