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

J Neuroimmunol. 2018 Jan 15:314:24-29. doi: 10.1016/j.jneuroim.2017.11.004. Epub 2017 Nov 8.

Abstract

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.

Keywords: CBLB; Gene; Interferon-beta; LMP7; Multiple sclerosis; TYK2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / blood
  • Adaptor Proteins, Signal Transducing / drug effects
  • Adjuvants, Immunologic / therapeutic use
  • Adult
  • Cytokines / blood*
  • Cytokines / drug effects*
  • Cytokines / immunology
  • Down-Regulation
  • Female
  • Humans
  • Interferon-beta / therapeutic use*
  • Male
  • 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 Kinase / blood
  • TYK2 Kinase / drug effects

Substances

  • Adaptor Proteins, Signal Transducing
  • Adjuvants, Immunologic
  • Cytokines
  • Interferon-beta
  • CBLB protein, human
  • Proto-Oncogene Proteins c-cbl
  • TYK2 Kinase
  • TYK2 protein, human
  • LMP7 protein
  • Proteasome Endopeptidase Complex