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 GRα 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 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). 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 GRα (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 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.

FKBP5 activates mitophagy by ablating PPAR-γ to shape a benign remyelination environment

“…FKBP5 protein, a newly identified protein with an abnormal expression in MS progression, has been reported to accumulate in human MS (26,27), but it is not clear what the physiological role and mechanism of FKBP5 are in CPZ pathogenesis. In this study, we found that FKBP5 is crucial for the progression of myelin loss and regeneration by activating the PINK1-Parkin mitophagy pathway, in which the important regulator, PPAR-γ, is critically regulated by FKBP5.…”

“…Mitophagy is one of the molecular mechanisms that have been linked to MS. Recent studies have found that the FKBP5 levels in the cerebrospinal fluid and peripheral blood of MS patients were significantly upregulated, suggesting that FKBP5 plays an important role (26,27). However, few studies have focused on mitophagy regulation by FKBP5 in demyelinating diseases.…”

Recent progress in epidemiology, clinical features, and therapy of multiple sclerosis in China

“…The second-line therapy is plasma exchange. 272 A study explored the factors associated with the efficacy of glucocorticoid in Chinese patients with MS. 273 The results showed that patients who were sensitive to glucocorticoid had higher expression of glucocorticoid receptor (GR)-α and lower expression of FK506 binding protein 5 (FKBP5), which might provide a novel therapeutic strategy for glucocorticoid-resistant patients with MS in the acute stage.…”