Predicting glucocorticoid resistance in multiple sclerosis relapse via a whole blood transcriptomic analysis.
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BORIS DOI
Publisher DOI
PubMed ID
37817393
Description
AIMS
Treatment of multiple sclerosis (MS) relapses consists of short-term administration of high-dose glucocorticoids (GCs). However, over 40% of patients show an insufficient response to GC treatment. We aimed to develop a predictive model for such GC resistance.
METHODS
We performed a receiver operating characteristic (ROC) curve analysis following the transcriptomic assay of whole blood samples from stable, relapsing GC-sensitive and relapsing GC-resistant patients with MS in two different European centers.
RESULTS
We identified 12 genes being regulated during a relapse and differentially expressed between GC-sensitive and GC-resistant patients with MS. Using these genes, we defined a statistical model to predict GC resistance with an area under the curve (AUC) of the ROC analysis of 0.913. Furthermore, we observed that relapsing GC-resistant patients with MS have decreased GR, DUSP1, and TSC22D3 mRNA levels compared with relapsing GC-sensitive patients with MS. Finally, we showed that the transcriptome of relapsing GC-resistant patients with MS resembles those of stable patients with MS.
CONCLUSION
Predicting GC resistance would allow patients to benefit from prompt initiation of an alternative relapse treatment leading to increased treatment efficacy. Thus, we think our model could contribute to reducing disability development in people with MS.
Treatment of multiple sclerosis (MS) relapses consists of short-term administration of high-dose glucocorticoids (GCs). However, over 40% of patients show an insufficient response to GC treatment. We aimed to develop a predictive model for such GC resistance.
METHODS
We performed a receiver operating characteristic (ROC) curve analysis following the transcriptomic assay of whole blood samples from stable, relapsing GC-sensitive and relapsing GC-resistant patients with MS in two different European centers.
RESULTS
We identified 12 genes being regulated during a relapse and differentially expressed between GC-sensitive and GC-resistant patients with MS. Using these genes, we defined a statistical model to predict GC resistance with an area under the curve (AUC) of the ROC analysis of 0.913. Furthermore, we observed that relapsing GC-resistant patients with MS have decreased GR, DUSP1, and TSC22D3 mRNA levels compared with relapsing GC-sensitive patients with MS. Finally, we showed that the transcriptome of relapsing GC-resistant patients with MS resembles those of stable patients with MS.
CONCLUSION
Predicting GC resistance would allow patients to benefit from prompt initiation of an alternative relapse treatment leading to increased treatment efficacy. Thus, we think our model could contribute to reducing disability development in people with MS.
Date of Publication
2024-02
Publication Type
Article
Subject(s)
Keyword(s)
glucocorticoid glucocorticoid receptor multiple sclerosis resistance
Language(s)
en
Contributor(s)
Massy, Marine | |
Karathanassis, Dimitris | |
Evangelopoulos, Maria-Eleptheria |
Series
CNS neuroscience & therapeutics
Publisher
Wiley
ISSN
1755-5949
Access(Rights)
open.access