Down-regulation of TYK2, CBLB and LMP7 genes expression in relapsing-remitting multiple sclerosis patients treated with interferon-beta

• Published in: Journal of neuroimmunology Vol. 314; pp. 24 - 29
• Main Authors: Mazdeh, Mehrdokht, Moradi, Najmeh, Khoshroo, Elnaz, Shayesteh, Zahra, Taheri, Mohammad, Sayad, Arezou, Omrani, Mir Davood, Hajilooi, Mehrdad, Roshanaei, Ghodratollah, Solgi, Ghasem
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.01.2018
• Subjects: Adaptor Proteins, Signal Transducing - blood; Adaptor Proteins, Signal Transducing - drug effects; Adjuvants, Immunologic - therapeutic use; Adult; CBLB; Cytokines - blood; Cytokines - drug effects; Cytokines - immunology; Down-Regulation; Female; Gene; Humans; Interferon-beta; Interferon-beta - therapeutic use; LMP7; Male; Multiple sclerosis; Multiple Sclerosis, Relapsing-Remitting - blood; Multiple Sclerosis, Relapsing-Remitting - drug therapy; Multiple Sclerosis, Relapsing-Remitting - immunology; Proteasome Endopeptidase Complex - blood; Proteasome Endopeptidase Complex - drug effects; Proto-Oncogene Proteins c-cbl - blood; Proto-Oncogene Proteins c-cbl - drug effects; TYK2; TYK2 Kinase - blood; TYK2 Kinase - drug effects; Multiple sclerosis; CBLB; Interferon-beta; TYK2; LMP7; Gene
• ISSN: 0165-5728; 1872-8421; 1872-8421
• DOI: 10.1016/j.jneuroim.2017.11.004

This study aimed to examine the expression of TYK2, CBLB and LMP7 genes at both mRNA and protein levels in relapsing-remitting MS (RRMS) patients in compare with healthy controls. Seventy-eight RRMS patients treated with IFNβ-1a and 79 age- and ethnic-matched healthy subjects were studied. The mRNA expression levels of TYK2, CBLB and LMP7 in PBMCs were quantified by real-time PCR and plasma concentrations of three molecules were measured by ELISA. Results were compared between patients and controls, IFNβ-responders and non-responders. Forty-nine of 78 patients were classified as IFNβ-responders and 29 cases were non-responders. Significantly down-regulated expression of TYK2, CBLB and LMP7 genes was found in the patients group versus controls (P<0.001). Decreased plasma levels of three molecules were observed in patients compared to controls (P<0.001). IFNβ-responders had significantly higher expressions for CBLB (P=0.001) and LMP7 (P=0.02) than non-responders. Also, we observed increased expressions of LMP7 (P=0.39) and CBLB (P=0.02) genes in patients under 30y and increased expression of TYK2 in patients >40years (P=0.002). Our results suggest that expression analysis of TYK2, CBLB and LMP7 genes could be useful for evaluation of T cells immunity and clinical response to IFNβ-therapy in RRMS patients. IFNβ-responder (R) group of the RRMS patients had higher expressions for CBLB (P=0.001), LMP7 (P=0.02) and TYK2 (P=0.60) genes than non-responders (NR). Similarly, this difference was statistically significant at protein levels for LMP7 and CBLB molecules. [Display omitted] •TYK2, CBLB, and LMP7 molecules play key role in T cell activation and regulation of cellular responses.•Down-regulated expression of TYK2, CBLB and LMP7 genes was found in RRMS patients versus controls.•Decreased plasma levels of three molecules were observed in patients compared to controls.•IFNβ-responders had higher expressions for TYK2, CBLB and LMP7 genes than non-responders.•Expression analysis of TYK2, CBLB and LMP7 genes could be useful for evaluation of T cells immunity in RRMS patients.