Differential gene expression in antigen stimulated whole blood from patients with Tuberculosis and Tuberculosis-Diabetes comorbidity — ASN Events
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  3. Differential gene expression in antigen stimulated whole blood from patients with Tuberculosis and Tuberculosis-Diabetes comorbidity

Differential gene expression in antigen stimulated whole blood from patients with Tuberculosis and Tuberculosis-Diabetes comorbidity (#395)

Happy Tshivhula 1 , Léanie Kleynhans 1 , Gerhard Walzl 1 , Katharina Ronacher 1 2
  1. DST/NRF Centre of Excellence in Biomedical Tuberculosis Research and SA MRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg,, Cape Town, Western Cape, South Africa
  2. Mater Research Institute-The University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia

INTRODUCTION: Patients with tuberculosis-diabetes co-morbidity (TB-DM) are more likely to fail TB treatment compared to TB patients without co-morbidities1 despite having higher circulating concentrations of Th1 and Th17 cytokines2.  The aim of this study was to characterize antigen-specific immune responses in TB and TB-DM patients.

METHODS: Whole blood from patients with TB (n=10) and TB-DM (n=11) at baseline and end of treatment (month 6) were stimulated with Mycobacterium tuberculosis (Mtb) antigen cocktail (ESAT-6, CFP-10 and TB 7.7) and differential expression of 594 genes involved in immune regulation were determined using the Nanostring technology.

RESULTS: We demonstrate that genes associated with innate and adaptive immune cell types are differentially represented in unstimulated and antigen stimulated whole blood from TB and TB-DM patients’ at baseline and month 6. At baseline, unbiased hierarchical clustering showed clear separation of TB-DM from TB patients based on whole blood mRNA expression profiles. Genes involved in Jak-Stat signalling pathways were significantly up-regulated in TB-DM compared to TB patients, whereas genes involved in the iNOS and IL-12 signalling pathways were down-regulated.

CONCLUSION: Our results show differential gene expression and activation of immunological pathways in TB-DM compared to TB patients after stimulation with Mtb antigens. Alterations of these immunological pathways could be contributing factor in delayed Mtb clearance and unfavourable TB treatment outcomes in TB-DM patients and offer targets for host-directed therapeutic approaches to treat TB-DM co-morbidity.

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