The effect of glatiramer acetate, IFNβ-1a, fingolimod, and dimethyl fumarate on the expression of T-bet, IFN-γ, and MEG3 in PBMC of RRMS patients
The effect of glatiramer acetate, IFNβ-1a, fingolimod, and dimethyl fumarate on the expression of T-bet, IFN-γ, and MEG3 in PBMC of RRMS patients
Rozhin Dabbaghi,1,*Reza Safaralizadeh,2Shima Rahmani,3Behzad Baradaran,4
1. Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz 2. Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz 3. Immunology Research Center Tabriz University of Medical Sciences 4. Immunology Research Center, Tabriz University of Medical Sciences
Introduction: Autoreactive T helper type 1 (Th1) cells have been implicated in the pathogenesis of multiple sclerosis (MS). T-bet is one of the essential transcription factors in regulating the differentiation of Th1.
Methods: In this study, we investigated the expression level of T-bet, interferon-gamma (IFN-γ), and maternally expressed gene 3 (MEG3) in the peripheral blood mononuclear cells (PBMCs) of 5 treatment-naïve relapsing-remitting multiple sclerosis (RRMS) patients, 20 healthy controls, and 52 RRMS patients who have been treated with four different disease-modifying therapies (DMTs), i.e., glatiramer acetate (GA), interferon beta-1a (IFNβ-1a), fingolimod, and dimethyl fumarate (DMF).
Results: Our results have indicated that T-bet is substantially upregulated in treatment-naïve RRMS patients compared to healthy individuals. Besides, the expression levels of T-bet and MEG3 have been remarkably downregulated in IFNβ-1a and fingolimod-treated RRMS patients compared to treatment-naïve RRMS patients, respectively. The differential expressions have been more considerable in females. Moreover, our results have highlighted the diagnostic value of T-bet in RRMS. Although our study has shown a moderate positive correlation between T-bet and MEG3 in healthy individuals, a moderate positive correlation between IFN-γ and T-bet in healthy individuals, a strong positive correlation between MEG3 and IFN-γ in GA-treated RRMS patients, and a remarkable positive correlation between T-bet and MEG3 in DMF-treated RRMS patients,
Conclusion: Further studies are needed to investigate the cross-talk between MEG3, T-bet, and IFN-γ in RRMS patients.