Abstract

BackgroundGlucocorticoid (GC) is the first-line therapy in acute attacks of multiple sclerosis (MS), but its efficacy is individually variable and may be associated with glucocorticoid receptor (GR) gene.ObjectiveTo establish the association between GR gene sequence and clinical GC sensitivity in Chinese MS patients. And to investigate the expression differences of serum GRα and FK506 binding protein 5 (FKBP5) in GC responders and non-responders.Materials and methodsCoding exons 2–9 of the GR gene from 97 MS patients were sequenced. We performed ELISA to detect serum GRα and FKBP5 before the GC impulse therapy in patients with different GC sensitivities (according to the EDSS changes before and after the GC medication).ResultsSeven new mutations were located in exon 2, but the presence or absence of mutations was not associated with the response to GC therapy (P = 0.416). The GC-sensitive patients had higher GRα (P = 0.011) but lower FKBP5 (P = 0.025) levels in the serum.ConclusionsThe GR mutations detected in our study were not associated with the response to GC in Chinese MS patients. Higher GRα and lower FKBP5 levels in the serum might predict the response to GC, which may provide potential therapeutic target for GC-resistant patients with acute MS attack.

Highlights

  • Multiple sclerosis (MS) is an inflammatory disease of central nervous system (CNS) which generally begins in early adulthood

  • Researches in Caucasians report that polymorphisms of glucocorticoid receptor (GR) result in a modified transcript, which may have an impact on GC sensitivity and disease course [9,10,11]

  • We investigated the differences in GRα and FK506-binding protein 5 (FKBP5) concentrations in GC responders and non-responders to explore possible strategies for modulation of glucocorticoid reactivity

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Summary

Introduction

Multiple sclerosis (MS) is an inflammatory disease of central nervous system (CNS) which generally begins in early adulthood. Some patients were resistant to GC initially, but in some other patients, the response to GC attenuated with. The mechanism governing the responsiveness of GC action remains elusive [4, 5]. Multiple factors can influence cellular glucocorticoid sensitivity at the level of the glucocorticoid receptor (GR) and its signaling pathway, including cochaperones such as FK506-binding protein 5 (FKBP5) [6, 7]. Glucocorticoid (GC) is the first-line therapy in acute attacks of multiple sclerosis (MS), but its efficacy is individually variable and may be associated with glucocorticoid receptor (GR) gene

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