Investigating the TANK-binding kinase expression in multiple sclerosis patients in comparison with control group in the Iranian population

Abstract

Introduction: Multiple sclerosis (MS) is one of the most common inflammatory autoimmune diseases in the central nervous system, which affects individuals ranged between 20 and 40 years of age. There is still no gene or genes set that is unique to the disease. On the other hand, TANK-binding kinase 1 (TBK1) gene is one of the most important interferon signalling molecules and has been shown to affect many autoimmune diseases, and it is obvious that it is involved in CNS inflammation. In this study, we investigated the expression of TBK1 gene as a major factor in the production and activity of interferons in patients with MS. Materials and Methods: Ninety patients with MS and 30 healthy individuals referring to Kashani Hospital in Shahrekord which matched for age and sex were selected. According to the received treatments, MS patients were divided into three groups as follows: the newly diagnosed group not receiving treatment, interferon β1α (IFNβ1α) treatment group and IFNβ1β treatment group. After filling the questionnaire, blood was sampled, total RNA was extracted and finally, cDNA was synthesised from the individuals. The TBK1 kinase gene expression was investigated using the TaqMan real-time with ΔΔCt method. Obtained data were analysed using GRAPHPAD 5 and SPSS version 21 software. Results: In this study, the two studied groups did not show any significant differences in age and sex parameters. Our results showed that TBK1 expression in newly diagnosed patients was significantly higher than the control group (P < 0.006). However, no significant difference was observed between the two treated groups with the control group. Furthermore, there was a significant difference at the TBK1 gene expression level between the newly diagnosed group patients and the two groups receiving the treatments. There was also no significant correlation between age and sex with gene expression was demonstrated in this study (P = 0.130 and P = 0.310, respectively). Conclusion: Disruption of TBK1 gene expression can be one of the MS causes of onset at the molecular level. Besides, since the expression of this gene has been investigated in newly diagnosed individuals with MS, it may be possible to utilise this molecule in the early detection of the disease, especially in individuals at high risk of disease (with risk index). It can also be used as a new therapeutic approach by targeting this molecule to improve the progression of disease; furthermore, it can be used as a factor in responding to treatment in patients responding to IFN.

Keywords

• autoimmune disease
• interferon
• multiple sclerosis
• tank-binding kinase 1 gene