Dataset Information

Glucocorticoid receptor mutations and clinical sensitivity to glucocorticoid in Chinese multiple sclerosis patients.

ABSTRACT: BACKGROUND: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. OBJECTIVE:To establish the association between GR gene sequence and clinical GC sensitivity in Chinese MS patients. And to investigate the expression differences of serum GR? and FK506 binding protein 5 (FKBP5) in GC responders and non-responders. MATERIALS AND METHODS:Coding exons 2-9 of the GR gene from 97 MS patients were sequenced. We performed ELISA to detect serum GR? and FKBP5 before the GC impulse therapy in patients with different GC sensitivities (according to the EDSS changes before and after the GC medication). RESULTS:Seven 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 GR? (P?=?0.011) but lower FKBP5 (P?=?0.025) levels in the serum. CONCLUSIONS:The GR mutations detected in our study were not associated with the response to GC in Chinese MS patients. Higher GR? 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.

SUBMITTER: Song T

PROVIDER: S-EPMC7478945 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Glucocorticoid receptor mutations and clinical sensitivity to glucocorticoid in Chinese multiple sclerosis patients.

Song Tian T Chang Haoxiao H Du Li L Yin Linlin L Shi Fudong F Zhang Xinghu X

Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 20200410 10

<h4>Background</h4>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.<h4>Objective</h4>To 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.<h4>Materials and methods</h4>Co ...[more]

PMID: 32277392

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Project description:Multiple sclerosis (MS) is an autoimmune disease that leads to the demyelination of nerve axons. An increasing number of studies suggest that patients with MS exhibit altered metabolic profiles, which might contribute to the course of MS. However, the alteration of metabolic profiles in Chinese patients with MS and their potential roles in regulating the immune system remain elusive. In this study, we performed a global untargeted metabolomics approach in plasma samples from 22 MS-affected Chinese patients and 21 healthy subjects. A total of 42 differentially abundant metabolites (DAMs) belonging to amino acids, lipids, and carbohydrates were identified in the plasma of MS patients and compared with those in healthy controls. We observed an evident reduction in the levels of amino acids, such as L-tyrosine, L-isoleucine, and L-tryptophan, whereas there was a great increase in the levels of L-glutamic acid and L-valine in MS-affected patients. The levels of lipid and carbohydrate metabolites, such as sphingosine 1-phosphate and myo-inositol, were also reduced in patients with MS. In addition, the concentrations of proinflammatory cytokines, such as IL-17 and TNF-α, were significantly increased, whereas those of several anti-inflammatory cytokines and chemokines, such as IL-1ra, IL-7, and MIP-1α, were distinctly reduced in the plasma of MS patients compared with those in healthy subjects. Interestingly, some DAMs, such as L-tryptophan and sphingosine 1-phosphate, showed an evident negative correlation with changes in the level of TNF-α and IL-17, while tightly positively correlating with altered concentrations of anti-inflammatory cytokines and chemokines, such as MIP-1α and RANTES. Our results revealed that altered metabolomic profiles might contribute to the pathogenesis and course of MS disease by modulating immuno-inflammatory responses in the peripheral system, which is essential for eliciting autoimmune responses in the central nervous system, thus resulting in the progression of MS. This study provides potential clues for developing therapeutic strategies for MS in the near future.

Dataset Information

Glucocorticoid receptor mutations and clinical sensitivity to glucocorticoid in Chinese multiple sclerosis patients.

Publications

Glucocorticoid receptor mutations and clinical sensitivity to glucocorticoid in Chinese multiple sclerosis patients.

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